3,139,421 United States Patent Office Patented June 30, 1964

1. 2 zinyl, thiazinyl, triazolyl, oxadiazolyl, thiadiazolyl, di 3,139,421 oxanyl, oxathiolyl, oxadiazolyl, dithiinyl, oxathiinyl, py AZO, COMPOUNDS AND METHODS FOR ranyl, thiapyranyl, pyridyl, pyrimidyl, pyridazinyl, pyra PRODUCING SAME zinyl, or the tetrazolyl radicals, their N-oxides and benzo-, Edward F. Elslager, Donald F. Worth, David B. Capps, 5 and naphtho-condensed ring systems. and Leslie M. Werbel, all of Ann Arbor, Mich., as In accordance with the invention, the novel 4-(dialkyl signors to Parke, Davis & Company, Detroit, Mich., a aminoalkylamino)-1-naphthylazo heterocyclic compounds corporation of Michigan No Drawing. Filed Mar. 14, 1960, Ser. No. 14,523 of the above formula and their acid-addition salts can be 6 Claims. (Cl. 260-154) produced in a number of ways. 10 For example, the products of the invention can be pre This invention relates to a novel class of azo com pared by coupling an a-naphthylamine having in free base pounds and salts thereof and to methods for obtaining form the formula same. More particularly, it relates to novel 4-(dialkyl aminoalkylamino)-1-naphthylazo heterocyclic compounds and non-toxic acid-addition salts thereof which possess 5 anti-parasitic activity. R The novel 4 - (dialkylaminoalkylamino)-1-naphthylazo heterocyclic compounds with which the present invention (I) is concerned have in their free base form the formula with a diazonium compound of the formula 20 N=N-HET--Ac In the above formula Act represents the anion of an acid or the OH ion and R, Y, and HET have the same mean ing as given above. Preferably, the reaction is conducted 25 under acidic or neutral conditions (pHs7), although if desired, basic conditions can be employed. In carrying N=N-HET out this condensation it is generally satisfactory to em where Y represents a radical of the formula ploy substantially equivalent quantities of the reactants R in the presence of a suitable solvent. Suitable solvents 30 for the reaction are aqueous mixtures of water-miscible -A-N aliphatic alcohols, such as methanol, ethanol and pro R; panol; tetrahydrofuran, N,N-dimethylacetamide, N,N-di or a radical of the formula methylformamide, simple organic acids such as formic (CE) acid, acetic acid, propionic acid and the like; or the acid 35 furnishing the anion represented by Act. Where it is desired to carry out the reaction at a controlled pH, a (CH), suitable buffer system may be employed. In general, the A represents an alkylene radical containing between 2 and time and temperature of the reaction are not critical; 8 carbon atoms inclusive, or an alkylene radical contain however, heating is to be avoided, and a temperature less ing more than 2 and less than 7 carbon atoms in which 40 than 15 C. is preferred. one of the methylene groups not attached to the nitrogen The diazonium compounds of the above formula can atoms is replaced by -O-, -S-, -CHOH, =COH be conveniently prepared in situ, by the reaction of an (lower alkyl), -N (lower alkyl) or =CH (dilloweralkyl amine of the formula aminoalkyl); R represents hydrogen, a lower alkyl radical, a halogen atom, or a lower alkoxy radical, said NH-HET R group can be attached to the 5th, 6th, or 7th positions 45 with an alkali nitrite such as e.g. sodium nitrite in an acid of the naphthylene nucleus; R1 and R2 each represents an medium (pH <7) or by other methods known to organic alkyl radical, a cycloalkyl radical, a hydroxyalkyl radical, chemists, and added to the coupling reaction mixture or an alkoxyalkyl, said radicals containing fewer than 7 containing the desired a-naphthylamine of Formula I. carbon atoms, the allyl or methallyl radicals, or a lower The a-naphthylamines of the Formula I employed as dialkylaminoalkyl radical containing 3 to 7 carbon atoms 50 starting materials in this reaction can be prepared in vari inclusive, or in combination with -NC represent a ous ways. heterocyclic radical having fewer than 10 carbon atoms For example, they can be prepared by aminoalkylation such as e.g. a pyrrolidyl, piperidinyl, hexamethylene of an a-naphthylamine of the formula iminyl, morpholinyl, piperazinyl, homopiperazinyl or dec ahydroquinolyl radical, said heterocyclic radical option 55 NH ally bearing lower alkyl, lower hydroxyalkyl, lower al koxyalkyl, hydroxy, lower alkoxy, amino, or lower di alkylaminoalkyl substituents; if represents an integer from 0 to 3 inclusive, g and h represent integers such that g--h=3 or 4; R represents a lower alkyl, lower hydroxy 60 alkyl, lower alkoxyalkyl, or a lower dialkylaminoalkyl or an alkali metal salt thereof with an aminoalkylating radical; and HET represents a heterocyclic radical of agent of the formula fewer than 15 carbon atoms, a carbon atom of which is R1 bound to the azo nitrogen atom, said heterocyclic radical X-A-N may carry one or more substituents such as keto, hydroxy, 65 lower alkyl, lower hydroxyalkyl, lower aminoalkyl, halo, R phenoxy, acyl, sulfo, carboxy, thio, sulfonamido, sulfonyl, or of the formula imino, phenyl, lower alkoxy, nitro, or amino radicals. (CH) Examples of suitable heterocyclic radicals are the furyl, thienyl, pyrryl, pyrazolyl, imidazolyl, thiazolyl, isothia O Z-(CH) -c?i 'N-R, zolyl, oxazolyl, isooxazolyl, hexamethyleneiminyl, oxa (CH), 3,139,421 w 3 a. 4. wherein X represents a halogen atom or the The reaction is favored by temperatures of 100-175 C. CH-CH and is preferably carried out in a sealed container in an aqueous medium and in the presence of an agent such as group; Z represents a halogen atom, and A, R, R1, R2, R3, sulfur dioxide, sodium bisulfite or sodium hydrosulfite. f, g and h have the aforementioned significance. The re In the above formulas A, R, R1, R2, R3, f, g, and h have action proceeds readily in a solvent medium. Suitable the aforementioned significance. solvents for the reaction are benzene, toluene, and the Another process for the preparation of the compounds like. Where the free base form is employed the reaction of the invention comprises reacting an azo compound of is preferably conducted in the presence of a base such as the formula an alkali-metal carbonate, for example, potassium car O bonate. NH-A-Eal a-Naphthylamines of Formula I can also be prepared by reduction of a Schiff base having the formula H(or lower alkyl) 5 R. N-N-HET N with an amine of the formula 20 -CO R R The reduction can be conveniently effected by hydrogena Y, tion in the presence of a noble metal catalyst, such as 25 e.g. 20% palladium on charcoal. The Schiff bases of the wherein Hal represents a hologen atom and A, R, R1, R2, above formula can be readily prepared by condensation and HET are defined as hereinbefore. The reaction is of an aminoaldehyde or ketone of the formula preferably carried out in a solvent medium. Some suit O R1 able solvents for this purpose are aliphatic alcohols such (or lower alkyl)-C-B-N / as ethanol, isopropanol, pentanol, glycols or the amine 30 employed in the reaction. The relative proportions of the R reactants is not critical; however, best results are obtained and an a-naphthylamine of the formula when an excess of the amine is employed. The reaction is favored by temperatures in excess of 50 C. and prefer NH 35 ably carried out between 50 and 150° C. The azo compounds of the above formula employed as starting materials in this reaction are conveniently prepared by the coupling of a compound of the formula (O 40 NE-A-Hal in a solvent medium. Suitable solvents for the reaction are benzene, toluene and the like. The reaction is favored by an acid catalyst such as e.g. p-toluene sulfonic acid, and by temperatures in excess of 50° C. and is preferably carried out between 50 and 150° C. The Schiff bases so (II) formed can be reduced catalytically without isolation or 45 purification from the reaction mixture. In the above with a diazonium compound of the formula formulas R, R and R2 have the aforementioned signif icance and B represents an alkylene radical containing N=N-HET--Act between 2 and 7 carbon atoms inclusive, or an alkylene wherein Hal, A, R, and HET have the aforementioned radical containing more than 2 and less than 6 carbon 50 significance and Act represents the OH ion or the anion atoms in which one of the methylene groups not attached of a hydrohalic acid. Preferably, the reaction is con to the nitrogen atoms is replaced by -O-, -S-, ducted under acidic or neutral conditions (pH s7), al =CHOH, =CH(dialkylaminoalkyl) or =NClower though if desired, basic conditions can be employed. In alkyl). carrying out this condensation it is satisfactory to employ Additionally, the a-naphthylamines of Formula I can 55 substantially equivalent quantities of the reactants in the be prepared by a replacement reaction between a com presence of a suitable solvent. Suitable solvents for the pound of the formula reaction are aqueous mixtures of water-miscible aliphatic R alcohols, such as methanol, ethanol and propanol; tetra M hydrofuran, N,N-dimethylacetamide; simple organic acids H2N-A-N 60 such as formic acid, acetic acid, propionic acid and the R like; or an excess of the acid furnishing the anion rep or of the formula resented by Act. Where it is desired to carry out the reaction at a controlled pH, a suitable buffer system may (CII) be employed. In general, the time and temperature of HN-(CH2) -CH N-R, 65 the reaction are not critical; however, heating is to be (CH2) avoided, and a temperature less than 15 C. is preferred. The diazonium compounds of the above formula can and the hydroxyl group on an a-naphthol of the formula be conveniently prepared in situ, by the reaction of an amine of the formula OH 70 NH-HET with an alkali metal nitrite such as e.g. sodium nitrite in an acid medium (pH <7) or by other methods known to organic chemists, and added to the coupling reaction mix ture containing the desired compound of Formula IF. 3,139,421 5 6 The compounds of the invention can also be produced converting the said amino compound to a diazonium by hydrolysis of a compound of the formula compound, and coupling the said diazonium compound with a suitable heterocyclic compound. In the above formulas Y, R and R have the aforementioned sig nificance. Where R represents the perhaloalkyl group such as e.g. trifluoromethyl, the acylation reaction is con veniently effected by employing the acid anhydride in a solvent medium such as e.g. N,N-dimethylformamide. Where R represents a hydrogen atom, acylation is prefer O ably effected using a formic acid-acetic-anhydride mix Ns N. HET ture. Acylation with the latter agent is favored by in creased temperatures, preferably between 50-125 C., wherein the group whereas the acylation using the perhaloalkanoic acid an O hydride proceeds readily at about 25-50 C. R-- The conversion of the free -NH group to the di 5 azonium salt proceeds readily under mild acidic condi is particularly susceptible to hydrolytic cleavage by acidic tions in the presence of an alkalinitrite such as e.g. sodium or basic hydrolytic agents under mild conditions. In the nitrite, preferably at a temperature under 15 C. The above formulas R represents the hydrogen atom or a per coupling of the diazonium salt and the heterocyclic com haloalkyl radical such as e.g. -CF3, and R, Y, and HET 20 ponent can be effected under basic or acidic conditions. have the aforementioned significance. Where R4 repre In general, where the heterocyclic component is acid sents a perhaloalkyl radical, the hydrolysis is preferably sensitive, the formamide derivative is employed and the effected by dissolving the starting material in a water coupling conducted under neutral or basic conditions miscible inert organic solvent such as methanol, adding (pH 27). Where the heterocyclic component is alkali an aqueous solution of an alkali metal hydroxide, con 25 sensitive, the coupling reaction is preferably conducted veniently and aqueous solution of sodium or potassium under acidic conditions (pH s7) and a perhaloalka hydroxide having a normality of about 1 to 3, and allow noylamide derivative, preferably the trifluroacetamide de ing the reaction mixture to stand (with or without stir rivative, is employed. The time and temperature of the ring) at about room temperature until the reaction is com coupling reaction are not critical, however, best results pleted. Where R represents the hydrogen atom, hy 30 are obtained when the reaction is allowed to proceed at drolysis is preferably conducted in the presence of a a temperature less than 15° C. Preferred solvent for the mineral acid such as e.g. hydrochloric acid under similar reaction is water or aqueous mixtures of water-miscible reaction conditions. alcohols such as methanol, ethanol, propanol and the The amides employed as starting materials in this proc like. If desired, after the coupling reaction has proceeded ess are novel per se and can be prepared by a process to completion, the azo-amide compounds can be hydro which comprises acylation of a nitro compound having izyed to the azo products of the invention without isola the formula tion or purification by adjusting the pH and temperature of the mixture to the preferred range. NH-Y As mentioned above, the compounds of the invention 40 possess valuable anti-parasitic properties. More partic R. ularly, the compounds are active against Schistosoma mansoni, a causative agent of schistosomiasis. They are active when administered orally. In addition, the com NO pounds of the invention are valuable intermediates in 45 the preparation of other valuable chemical compounds with an acid of the formula possessing anti-parasitic activity. The free bases encompassed herein can also be em ployed in the form of their addition salts with pharma ceutically acceptable acids, the term "pharmaceutically Ho-5-R, acceptable acids' designating acids capable of being em 50 ployed in the production of salts suitable for pharma or a functional derivative thereof to yield an amide of ceutical use even though, like irritant and corrosive acids, the formula they are not acceptable for pharmaceutical use in and O of themselves. The expression “salts with pharmaceuti 55 cally acceptable acids' refers to chemical structure rather R.--N-Y than to method of formation, and includes such salts whether formed by neutralization or other salt forming means. Some examples of the many organic and inorganic acids which can be used to produce the corre sponding acid-addition salts are hydrochloric, hydro 60 bromic, hydroiodic, sulfuric, phosphoric, oxalic, cholic, NO sulfanic, naphthalene-1,5-disulfonic, phenoxyacetic, lac tic, tartaric, gluconic, alginic, citric, succinic, maleic, subjecting said amide to hydrogenation in the presence malonic, adipic, mandelic, oleic, tannic, ethylsulfuric, of a catalyst such as e.g. Raney nickel to yield an amino penicillinic, benzoic, 5,5'-naphthalenedisalicylic, 3- and 5 compound of the formula 65 phenylsalicylic, 3-hydroxy-2-naphthoxy, 4,4'-methylene bis - (3-hydroxy-2-naphthoxy), 1,4,5,8 - naphthalene g tetracarboxylic, 4-biphenylcarboxylic, terephthalic, pyro R C mellitic, 8-hydroxy-7-iodo-5-quinolinesulfonic, cyclopen O tylpropionic, cyclohexanecarboxylic, arsanilic, arsonic acid and the like. Salts of the free bases of the invention with inorganic antimony derivatives such as e.g. antimony trichloride, and with compounds known to possess activity against schistosomiasis such as phthalic acid, mono-4-(3'- NH 75 chloro-4'-methylphenyl)-piperazide, maleic acid mono-4- 3,189,421 7 (3'-chloro. 4'-methylphenyl) - piperazide, pyridine-2,3- uracil, salt with one-half formula weight 4,4'-methylene dicarboxylic acid mono-4-(3'-chloro-4'-methylphenyl)- bis(3-hydroxy-2-naphthoic acid), of formula, piperazide, succinic acid mono-4-(3'-chloro-4'-methyl phenyl)-piperazide, oxalic acid mono-4-(3'-chloro-4'- NH(CII)N(CEI) methylphenyl) - piperazide, maleic acid mono-4-(3'- 5 bromo-4'-methylphenyl)-piperazide, adipic acid mono-4- .112 (3 - chloro - 4 - methylphenyl)-piperazide, glutaric acid mono - 4 - (3'-chloro - 4 - methylphenyl) - piperazide, terephthalic acid mono-4-(3'-chloro-4'-methylphenyl)- piperazide, diglycollic acid mono-4-(3'-chloro-4'-methyl O Y. ? phenyl)-piperazide, N,N'-heptamethylenebis - (oxy-p- phenylene)]-diglycine, N,N'-heptamethylenebis (oxy-p- IIO--OII phenylene) - di-b-alanine, heptamethylenebis-(oxy-p- phenylene nitrilo))-tetraacetic acid, and organic antimony derivatives such as 2-hydroxy-5-oxo-1,3,2-dioxastibiolane 15 4-glycolic acid, 2-(4,6-disulfo-1,3,2-benzodioxastibiol-2- yloxy)-1-phenyl-3,5-disulfonic acid, and antimony-2,3-di IOOC OE EO COO mercaptosuccinate are of particular interest. In like manner, the following related compounds can The invention is illustrated, but not limited, by the be prepared, starting from 5-aminouracil and an equiva following examples: 20 lent quantity of the appropriate 1-(dialkylaminoalkyl Example 1 amino)-naphthalene: A solution of 41.2 g. (0.325 mole) of 5-aminouracil in 11. of 50% ethanol and 85 ml. (1 mole) of concentrated 5-4-(2-dimethylaminoethylamino)-1-naphthylazol hydrochloric acid is cooled to 0° C. The amine is dia uracil zotized by the slow, portion-wise addition of a solution 2 5 5-4-(2-diisopropylaminoethylamino)-1-naphthyl of 22.4 g. (0.325 mole) of sodium nitrite in 200 ml. of azol-uracil water. The mixture is stirred 15 minutes at 0° C., then 5-4-(2-dibutylaminoethylamino)-1-naphthylazol added slowly at 0° to 5° C. to a solution of 78.7 g (0.325 uracil mole) of 1-(2-diethylaminoethylamino)-naphthalene in 5-4-(2-diisobutylaminoethylamino)-1-naphthaylazol 11. of 95% ethanol and sufficient concentrated hydro 30 uracil chloric acid to make the solution acidic to Congo red. 5-4-(3-dimethylaminopropylamino)-1-naphthylazol The deep purple solution which forms immediately uracil changes slowly to a green suspension as the hydrochloride 5-4-(3-diethylaminopropylamino)-1-naphthylazol salt begins to precipitate. The suspension is stirred about uracil 1 hour at 0° C. The pH is adjusted to approximately 35 5-4-(2-dimethylamino-1-methylethylamino)-1- 8 by the addition of sodium hydroxide solution and the naphthylazo-2,4-pyrimidinediol red product is collected by filtration. This is the desired The starting material, 1-(2-diethylaminoethylamino)- 5 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazol naphthalene, can be prepared as follows: a mixture of uracil, of formula 572 g. (4 moles) of 1-naphthylamine, 690 g. (4 moles) 40 of 2-diethylaminoethylchloride hydrochloride, 1250 g. (9 moles) of anhydrous potassium carbonate, 3 1. of ben zene and 20 g. of copper-bronze powder is stirred and boiled under reflux for 18 hours. The mixture is cooled NICH).N(C.H.), and 5 I. of 5% sodium hydroxide and 1 1. of ether are 45 added. The mixture is stirred vigorously for one-half hour, the layers are allowed to separate and the aqueous layer is siphoned off. The alkaline solution is extracted with several portions of ether, benzene or chloroform, and the combined organic extracts are added to the ben 50 zene-ether layer. The combined solvent mixture is washed twice with water, once with saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The drying agent is collected by filtration and the filtrate concentrated in vacuo on the steam bath. Vacuum dis Crystallization from ethanol gives shiny red crystals, M.P. 55 tillation of the residue through a 10-inch Vigreux column 210-211° C. (dec.). gives the desired 1-(2-diethylaminoethylamino)-naphthal The hydrochloride salt is prepared as follows: 3.3 g. ene as a pale yellow oil, B.P. 170-172 C./1.5 mm., of the base is dissolved in boiling ethanol and the solution n25 1.5903. is filtered into 200 ml. of ethanolic hydrogen chloride. The other intermediate 1-(dialkylaminoalkylamino)- The resulting deep purple suspension is heated to boil- 60 naphthalenes can be prepared by the procedures described ing and allowed to cool overnight. The dihydrochloride under Examples 1 through 15 herein. salt which precipitates is collected by filtration and dried Example 2 in vacuo at 65° C.; M.P. 200-203 C. The acid addition salt with 4,4'-methylenebis(3-hy A solution of 12.0 g (0.025 mole) of N-4-(2,6-di droxy-2-naphthoic acid) can be prepared according to the 65 amino - 3 - pyridylazo) - 1 - naphthyl - N - (2 - diethyl following procedure: 200 g. (0.5 mole) of 5-[4-(2-di aminoethyl)-ox,a,c-trifluoroacetamide is dissolved in 250 ethylaminoethylamino)-1-naphthylazo-uracil and 97 g. ml. of 2-propanol, filtered, and treated with 25 ml. (0.050 (0.25 mole) of 4,4'-methylenebis(3-hydroxy-2-naphthoic mole) of 2 N sodium hydroxide solution in methanol acid) are dissolved in 2.5 1. of dimethylformamide. The and 5 ml. of water. Stirring is continued for 25 hours, solution is cooled to approximately 10° C. and poured 70 after which time excess Dry Ice is added and the mixture slowly with vigorous stirring into 7.5 1. of cold water. is diluted with an ice and water mixture to a volume of 1 The precipitate is collected by filtration, washed thor 1. The precipitate is collected by filtration and the fil oughly with water and methanol, and dried in vacuo. The trate is concentrated to a volume of approximately 400 red salt thus obtained, M.P. 210-215 C., is the desired ml., during which process a precipitate appears. This is 5 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazol- 75 collected by filtration and combined with the previous 3,189,421 10 solid. This product is dissolved in 300 ml. of 2-propanol, methanol and 40 ml. of 1 N methanolic hydrogen chloride filtered, and the filtrate is concentrated to 250 ml. and and hydrogenated in the presence of 1 g. of Raney nickel treated with 12 ml. of a 2 N 2-propanolhydrogen chloride catalyst at 25-35 C. under 25-55 p.si.g. of hydrogen. mixture. The precipitate is collected by filtration and The catalyst is collected by filtration and the filtrate evapo crystallized from a dimethylformamide-2-propanol mix rated under reduced pressure to give a mushy crystalline ture. The black crystals thus obtained, M.P. 234 C. residue which is diluted with ether, filtered, and the (dec.), are the desired 2,6-diamino-3-4-(2-dimethyl precipitate washed thoroughly with ether. Crystallization aminoethylamino)-1-naphthylazolpyridine, monohydro from ethanol gives the desired N-(2-diethylaminoethyl)- chloride, of formula, N - (4-amino - 1 - naphthyl)-trifluoroacetamide, monohy NII (CII)N(CTIs) O drochloride as fine white needles, M.P. 216-218 C. To a stirred solution of 9.75 g. (0.025 mole) of N-(2- diethylaminoethyl) - N - (4-amino-1-naphthyl)-trifluoro acetamide, monohydrochloride, in 90 g. of water and ice containing 4.5 ml. of concentrated hydrochloric acid is 5 added 25 ml. of 1 M sodium nitrite over a period of 5 N=N. minutes. The mixture is stirred at 0° C. for 5 minutes HCl and added immediately to a solution of 2.8 g. (0.025 II,N--NII mole) of 2,6-diaminopyridine in 5.5 ml, of concentrated N hydrochloric acid and 275 g. of ice and water. After By a similar procedure, the following related compounds stirring for one hour at 1-12 C. and one hour at 12-18 can be prepared, starting from the appropriate 1-(alkyl C., a solution of 8 ml. of concentrated ammonium hy aminoalkylamino)-naphthalene via the N-(4-(heterocy droxide diluted to 100 ml. with water is added and the clicazo)-1-naphthyll-N-(alkylaminoalkylamino) - a,c,c- orange solid which separates is collected by filtration, trifluoroacetamides: washed with 200 ml. of water containing a few drops of 1-3-(4-(2,6-diamino-3-pyridylazo)-1-naphthylamino 25 concentrated ammonium hydroxide, and dried in vacuo. propyl)-piperidine, hydrochloride. This is the desired intermediate, N-(4-(2,6-diamino-3- 2,6-diamino-3-4-(3-diethylaminopropylamino)-1- pyridylazo)-1-naphthyl-N-(2-diethylaminoethyl) - a,a,c- naphthylazol-pyridine, hydrochloride. trifluoroacetamide. 2,6-diamino-3-4-(2-diethylaminoethylamino)-7-nitro The other N - (4 - pyridylazo-1-naphthyl)-N-(dialkyl 1-naphthylazol-pyridine, hydrochloride. 30 aminoalkyl)-a,c, ox-trifluoroacetamides are prepared in a 2,6-diamino-3-4-3-bis-(2-methoxyethyl-amino-2,2- similar manner from the appropriate aminopyridine and dimethylpropylamino-1-naphthylazo-pyridine, N - dialkylaminoalkyl-N-(4-amino-1-naphthyl)-a,c,d-tri hydrochloride. fluoroacetamide compounds. 4-amino-3-(4-(3-diethylaminopropylamino)-1-naph Alternatively, 2,6 - diamino-34-(2-diethylaminoethyl thylazol-2,6-pyridinediol, hydrochloride. 35 amino)-1-naphthylazol-pyridine, monohydrochloride and 2,4,6-triamino-3-(4-(2-diethylaminoethylamino)-1- related compounds can be prepared from N-(2-diethyl naphthylazopyridine, hydrochloride. aminoethyl)-N-(4-amino-1-naphthyl)-formamide accord 2-amino-6-(2-diethylaminoethoxy)-3-(4-(2-diethyl ing to the following procedure: A mixture of 3.5 ml. of aminoethylamino)-1-naphthylazol-pyridine, formic acid, 8.4 mi. of acetic anhydride, and 50 ml. of dihydrochloride. 40 tetrahydrofuran is heated on the steam bath for two hours. 4-2-1-(2-4-(2,6-diamino-3-pyridylazo)-1-naphthyl Upon cooling 5.74 g. (0.02 mole) of N,N-diethyl-N'- amino-ethyl-4-piperidyl-ethyl)-morpholine, (4-nitro-1-naphthyl)-ethylenediamine is added, and the dihydrochloride. resulting solution is stirred and heated under reflux for 24 hours. The solvent is removed in vacuo and the resi N - 4 - (2,6-diamino - 3 - pyridylazo) - 1 - naphthyl)- due suspended in excess aqueous sodium hydroxide solu N - (2 - diethylaminoethyl) - a,c,d. - trifluoroacetamide, 45 tion and extracted with ether. The ether extracts are employed as a starting material in the above procedure, is dried over anhydrous sodium sulfate, the drying agent is prepared as follows: a mixture of 46 g. (0.22 mole) of 1 collected by filtration, and the solvent removed in vacuo. chloro-4-nitronaphthalene and 77 g. (0.66 mole) of N,N- The residual yellow oil is the desired intermediate, N-(2- diethylethylenediamine is heated on the steam bath until diethylaminoethyl) - N - (4-nitro-1-naphthyl)-formamide, an exothermic reaction occurs. The temperature reaches 50 which is used directly in the next step without further 140 C., then drops slowly to 110° C., whereupon heating purification. is resumed for 2 hours. The hot melt is poured with stir The above formyl derivative is subsequently dissolved ring into 750 ml. of water containing 35 ml. of concen in 300 ml. of methanol and hydrogenated at an initial hy trated ammonium hydroxide and ice. The aqueous phase drogen pressure of 44 psi.g. in the presence of 1 g, of is separated, the residue triturated with warm water, and 55 Raney nickel catalyst. The catalyst is collected by filtra the residue crystallized from 2-propanol. This is the de tion and the solvent removed in vacuo. The residual oil sired intermediate, N,N-diethyl-N'-(4-nitro-1-naphthyl)- is cooled to room temperature, dissolved in 2-propanol, ethylenediamine, yellow platlets, M.P. 80-81 C. and treated with a 2-propanol-hydrogen chloride mixture Subsequently, a solution of 13.5 g. of trifluoroacetic until precipitation is complete. The crude product is col anhydride in 40 ml. of dimethylformamide is added to a 60 lected by filtration, washed with 2-propanol and dried in stirred solution of 14.4 g. of N,N-diethyl-N'-(4-nitro-1- vacuo at 40° C. for 14 hours. Rapid crystallization from naphthyl)-ethylenediamine in 90 ml. of dimethylform warm 2-propanol containing a slight excess of hydrogen amide over a period of 30 minutes. Stirring is continued chloride gives the intermediate N-(2-diethylaminoethyl)- for 1 hour and the reaction mixture is poured into 1 1. of N - (4-amino-1-naphthyl)-formamide, dihydrochloride, ice and water containing 150 ml. of 1 M sodium bicar 65 bonate solution. The mixture is extracted with three 2 l. 1% hydrate, as a lavender solid, M.P. 130-140° C. (dec.), portions of ether and the combined ether extracts are of formula, washed with water and dried over anhydrous magnesium O sulfate. The desiccant is collected by filtration and the EI-C-N (CH2)N(CH) ether is removed in vacuo to give the desired intermediate 70 N - (4 -nitro-1-naphthyl)-N-(2-diethylaminoethyl)-ox,a,a- trifluoroacetamide as a viscous oil, which is used directly in the subsequent reaction without further purification. The N-(2-diethylaminoethyl)-N-(4-nitro-1-naphthyl)- o,a,c-trifluoroacetamide (16 g.), is dissolved in 250 ml. of 75 N 3,139,421 11. 12 Subsequently, a cooled solution of 0.386 g. (0.0056 tities of the appropriate aminoindazole and 1-(dialkylami mole) of sodium nitrite in 50 ml. of water is added to a noalkylamino)-naphthalene: solution of 2.0 g. (0.0056 mole) of N-(2-diethylamino ethyl)-N-(4-amino-1-naphthyl)-formamide, dihydrochlo 5-4-(2-dimethylaminoethylamino)-1-naphthylazol ride in dilute hydrochloric acid. After a few minutes, the 6-4-3-(4-methoxypiperidino)-propylaminol-1-indazole diazonium salt solution is added at 0-5 C. with stirring naphthylazo-indazole to a solution of 0.612 g. (0.0056 mole) of 2,6-diamino 7-4-(2-diethylaminoethylamino)-1-naphthylazol pyridine in 100 ml. of water and 1.2 ml. of concentrated indazole hydrochloric acid. Stirring is continued for several min 6-(42-(butylmethylamino)-ethylamino)-1-naphthylazo utes and the reaction mixture is made alkaline with sodium O 2-methylindazole hydroxide solution. The red solid, which exhibits a green 5-4-(2-diethylaminoethylamino)-1-naphthylazol iridescence, is collected by filtration and dried in vacuo. indazole This is the desired intermediate, N-(4-(2,6-diamino-3- 5-(6-bromo-4-(3-diethylamino-2,2-dimethylpropylami pyridylazo)-1-naphthyl)-N-(2-diethylaminoethyl) - form no)-1-naphthylazo-indazole amide, of formula, 7-4-(2-diethylaminoethylamino)-1-naphthylazol-4- O indazolesulfonic acid I-C-NCH).N.C.L.), 6-4-(2-diethylaminoethylamino)-6-nitro-1-naphthylazo indazole 20 6-amino-7-4-(2-diethylaminoethylamino)-1-naphthyl azol-1H-indazole 6-4-(4-diethylaminocyclohexylamino)-1-naphthylazol 1H-indazole 4-4-2-(allylethylamino)-ethylamino]-1-naphthylazo 5-amino-1H-indazole n r -NII 5-(4-2-(4-methyl-1-piperazinyl)-ethylamino]-1-naph The intermediate N - 4-(2,6-diamino-3-pyridylazo)-1- thylazo)-1H-indazole naphthyl-N-(2-diethylaminoethyl)-formamide is allowed 1,1-diisopropyl-4-methyl-7 - (1-naphthyl) - diethylene to stand at room temperature for 18 hours in ethanolic triamine, employed as a starting material in the above hydrogen chloride. The mixture is concentrated and made 30 preparation, is readily prepared according to the following alkaline with aqueous sodium hydroxide. The resulting procedures: a solution of 1.1 kg. (25 moles) of ethylene maroon solid is collected by filtration, washed thoroughly oxide in 10 l. of 95% ethanol (kept at 0° C. to minimize with water, and crystallized from a mixture of dimethyl the evaporation of ethylene oxide) is added in a slow formamide and 2-propanol. The black crystals thus ob stream over a period of 3 hours to a solution of 3.25 kg. tained, M.P. 234° C. (dec.), are the desired 2,6-diamino (22.7 moles) of 1-naphthylamine in 15 1. of 95% ethanol 3 - 4 - (2-diethylaminoethylamino)-1-naphthylazol-pyri with stirring, maintaining the temperature at 0° C. dur dine, monohydrochloride and are identical with the mate ing the addition. The reaction does not appear to be rial obtained by the hydrolysis of N-(4-(2,6-diamino-3- exothermic and no color change is noted. After the addi pyridylazo) - 1 - naphthyl)-N-(2-diethylaminoethyl)-ox,a,c- tion is complete, the reaction mixture is allowed to stand trifluoroacetamide. 40 at room temperature for 16 hours and then boiled under Example 3 reflux for 3 hours. The volatile materials are removed in vacuo on the steam bath and the residue distilled in To a solution of 9.5 g. (0.084 mole) of 5-aminoinda high vacuo through an 8-inch Vigreux column to give zole in 200 ml. of ice water and 20 ml. of concentrated N - (2 - hydroxyethyl)-1-naphthylamine as a colorless hydrochloric acid is cautiously added with stirring 5.8 g. 45 syrupy liquid, B.P. 157-161° C./0.25 mm., which solidi (0.084 mole) of sodium nitrite in 100 ml. of cold water. fies in the receiver. A mixture of 1 kg. (5.35 moles) of The mixture is maintained at 0° C. during the addition. N-(2-hydroxyethyl)-1-naphthylamine and 9 l. of constant When the addition is complete, the diazonium salt mix boiling hydrobromic acid (48%) is boiled under reflux ture is stirred at 0° C. for 10 minutes and poured slowly for 24 hours with mechanical stirring. Reflux is adjusted with stirring into a solution of 27.5 g. (0.084 mole) of 50 so that approximately 500 ml. of the condensed hydro 1,1-diisopropyl-4-methyl - 7 - (1-naphthyl) - diethylenetri bromic acid-water mixture is collected during this period. amine in 250 ml, of water and 17.5 ml. of concentrated Upon cooling, the desired bromide, hydrobromide which hydrochloric acid. Stirring is continued for 2 hours at 0° separates is collected by filtration, the filter cake is sucked C. and the mixture is allowed to stand at room tempera dry, and the product is digested thoroughly by stirring ture for 14 hours. The reaction mixture is made strongly 55 with 3 1. of boiling 2-propanol. The occluded brown alkaline with 10% aqueous sodium hydroxide solution impurities dissolve and the off-white crystals are collected and the orange-red dye is collected by filtration, washed by filtration, washed with fresh cold 2-propanol and thoroughly with water and dried in vacuo at 40 C. for dried in vacuo at 50° C. for 24 to 48 hours; M.P. soften 18 hours. This is the desired 5-4-(2-(2-diisopropylami ing at 200° C., M.P. 208-211 C. noethyl)-methylaminol - ethylamino - 1 - naphthylazo 60 In a 2 1.3-necked flask is placed 166 g. (0.5 mole) of indazole, of formula, N-(2-bromoethyl)-1-naphthylamine, hydrobromide, 79 g. CH3 (0.5 mole) of N,N-diisopropyl-N'-methylethylenediamine, 138 g. (1.0 mole) of anhydrous potassium carbonate and 500 ml. of dimethylformamide. This mixture is stirred 65 and heated at 100° C. for 30 hours. Upon cooling, the reaction mixture is poured into 4 1. of water and the oil which separates is extracted thoroughly with ether. The combined ether extracts are dried over anhydrous potas 70 sium carbonate, the drying agent is collected by filtration, and the solvent removed in vacuo on the steam bath. orange crystals, M.P. 107-109 C. The residue is distilled in vacuo through an 8-inch Vigreux Utilizing the preparative methods described under Ex column to give the desired 1,1-diisopropyl-4-methyl-7-(1- amples 1 through 15 herein, the following related com naphthyl)-diethylenetriamine as a pale yellow oil, B.P. pounds can be prepared, starting from equivalent quan 75 153-157° C./0.3 mm., n25 1.5619. 3,189,421 13 14 Alternatively, a mixture of 166 g. (0.5 mole) of N-(2- 1-2-[4-(6-quinolylazo)-1-naphthylamino)-ethyl-3-pyr bromoethyl)-1-naphthylamine, hydrobromine, 79 g (0.5 rolidinol, hydrochloride mole) of N,N-diisopropyl-N'-methylethylenediamine, 138 3-diethylamino-3'-[4-(6-methoxy-8-quinolylazo)-1-naph g. (1.0 mole) of anhydrous potassium carbonate and 500 thylamino)-1,1'-(ethylimino)-di-2-propanol, hydrochlo ml. of toluene is stirred and boiled under reflux for 30 ride hours. Upon cooling, 1 1. of 10% aqueous sodium hy 5-[4-(2-diethylaminoethylamino)-1-naphthylazol-7-(di droxide solution is added and the mixture is stirred until ethylaminomethyl)-8-quinolinol, hydrochloride two distinct layers separate. The aqueous layer is 7-chloro-4-(4-diethylamino-1-methylbutylamino)-8-4-2- siphoned off and extracted with 100 ml. of fresh toluene. (ethylmethylamino)-ethylamino-1-naphthylazo The combined toluene extracts are dried over anhydrous O quinoline, hydrochloride potassium carbonate, the drying agent is collected by fil oz-Diethylamino-4-5-4-2-(diisopropylamino)-ethylami tration and the solvent evaporated in vacuo by means no-1-naphthylazo-2-quinolylamino-o-cresol, hydro of a rotary evaporator. Distillation of the residue in chloride vacuo through an 8-inch Vigreux column gives the de a-Diethylamino-4-8-4-(2-diethylaminoethylamino)-1- sired naphthylamine as a yellow oil, B.P. 149-151 C./0.2 15 naphthylazol-4-quinolylamino-o-cresol, hydrochloride mm., n25 1.5613. N,N - diethyl-2,2-dimethyl-N'-1-naphthyl-1,3-propane Xylene also serves as an excellent solvent. For exam diamine, employed as a starting material in the above ple, a mixture of 118 g. (0.36 mole) of N-(2-bromo procedure, can be prepared as follows: a mixture of 157 ethyl)- 1 - naphthylamine, hydrobromide, 126 g (0.80 g. (1.0 mole) of 6-diethylaminopivaldehyde, 143 g. (1.0 mole) of N,N-diisopropyl-N'-methyl-ethylenediamine, and 20 mole) of 1-naphthylamine, 1 g. of p-toluenesulfonic acid 500 ml. of xylene is stirred and boiled under reflux for and 400 ml. of benzene is boiled under reflux for 8 30 hours. Upon cooling, 1 l. of 10% aqueous sodium hours. The water which separates is removed through a hydroxide solution is added and the mixture is stirred Dean-Stark water trap. The benzene is removed in vacuo until the two layers separate. The aqueous layer is sepa on the steam bath, the residue is dissolved in 300 ml. of rated and extracted with 200 ml. of benzene. The com 25 methanol, and 5 g. of 20% palladium on charcoal catalyst bined benzene-xylene layers are dried over anhydrous is added. The resulting mixture is hydrogenated in a potassium carbonate and the solvent removed in vacuo. steel bomb at room temperature under an initial hydrogen Distillation of the residue in vacuo through an 8-inch pressure of 52 p.s.i.g. When hydrogenation is complete, Vigreux column gives the desired amine as a yellow oil, the solvent is removed in vacuo on the steam bath and B.P. 153-156° C./0.3 mm., n25 1.5621. 30 the residue is made strongly alkaline with 10% aqueous The other intermediate 1 - (dialkylaminoalkylamino)- sodium hydroxide solution. The oil which separates is naphthalenes employed herein can be prepared according extracted with benzene, the combined benzene extracts to the procedures described under Examples 1 through 15. are dried over anhydrous potassium carbonate and the benzene is removed in vacuo. The residue is distilled in Example 4 35 vacuo through a 10-inch Vigreux column to give the A solution of 4.4 g. (0.062 mole) of sodium nitrite in desired N,N- diethyl-2,2-dimethyl-N'-1-naphthyl-1,3-pro 40 ml. of water is cooled to 0° C. and is slowly added to panediamine as a pale yellow oil, B.P. 161° C./1.0 mm., a solution of 12.7 g. (0.062 mole) of 8-amino-5,6-dimeth n25 1.5790. oxyquinoline in 200 ml. of 50% ethanol and 17 ml. of The other intermediate 1-(dialkylaminoalkylamino)- concentrated hydrochloric acid, maintaining the tempera 40 naphthalenes employed in the above example are prepared ture at 0° C. This diazonium solution is subsequently according to the procedures described under Examples 1 added to a solution of 17.5 g. (0.62 mole) of N,N-diethyl through 15 herein. 2,2-dimethyl-N'-1-naphthyl-1,3-propanediamine in 200 ml. Example 5 of 95% ethanol which has been made strongly acidic to A mixture of 4.4 g. (0.01 mole) of N-(2-bromoethyl)- Congo red with concentrated hydrochloric acid. The 45 4-(3-dibenzofuranylazo)-1-naphthylamine and 50 ml. of mixture is stirred for 2 hours at 0° C. and 18 hours at piperidine is heated on the steam bath for one hour. The room temperature. The crude hydrochloride is collected red solution is poured into 1 1. of water and the product by filtration and crystallized from isopropanol. The de which precipitates is collected by filtration, washed sired 8-4-(3-diethylamino - 2,2-dimethylpropylamino)-1- thoroughly with water, and dried in vacuo at 55° C. for naphthylazo - 5,6-dimethoxyquinoline, trihydrochloride, 50 18 hours. Crystallization from acetone gives the desired of formula, 1-2-[4-(3-dibenzofuranylazo) - 1 - naphthylamino-eth yl)-piperidine, of formula,

NHCHCCHN(H, (CH) 55 E3

OCH 3HCl 60

/ N N 65 contains 1% moles of water of hydration and melts at 166-170° C. In like manner, the following related compounds can as glistening red crystals, M.P. 164-165 C. be prepared, starting from the appropriate 1-(dialkyl 70 Alternatively, N-(2-chloroethyl)- 4 - (3-dibenzofuranyl aminoalkylamino)-naphthalene and aminoquinoline: azo)-1-naphthylamine, M.P. 170-171. C., can be sub 2-8-4-2-(isopropylmethylamino)-ethylamino]-1-naph stituted for N-(2-bromoethyl)-4-(3-dibenzofuranylazo)-1- thylazoquinolyloxy-ethanol, hydrochloride naphthylamine in the above procedure. 5-4-(2-diethylaminoethylamino)-1-naphthylazo-8-meth Utilizing the preparative methods described under Ex ylquinoline, hydrochloride 75 amples 1 through 15 herein, the following related com 3,139,421 5 16 pounds can be prepared, starting from the appropriate 3-4-(3-pyridylazo)-1 -naphthylaminol -2-propanol, trihy furanN'-[4-(3-dibenzofuranylazo)-1-naphthyl-N,N-diethyl and 1-naphthylamine precursors: drochloride, monohydrate, of formula, ethylenediamine OH N'-(4-(2-dibenzofuranylazo)-1-naphthyl-N,N-diethyl ethylenediamine NHCH, HCHN (cit.) 5-4-(2-diethylaminoethylamino)-1-naphthylazo)-2-fu 5-I4-(2-diethylaminoethylamino)-1-naphthylazol-2-benrancarbamic acid, ethyl ester zofurancarboxylic acid N'-[4-(2-bromo-3-dibenzofuranylazo)-6-chloro-1-naph O 1-2-[4-(6,7,8,9-tetrahydro-3-dibenzofuranylazo)-1-naphthyl-N-isopropyl-N-methylethylenedia nine thylamino)-ethyl-1-pyrrolidine r O N4-(3-dibenzofuranylazo)-1-naphthyl-N,N-diethyl-2- 1-diethylamino-3-(1-naphthylamino)-2 - propanol, B.P. methyl-1,3-propanediamine 5 175-178 C./0.5 mm., employed as an intermediate in N'-(4-(8-acetyl-3-dibenzofuranylazo)-7-methoxy-1-naph the above procedure, is prepared from 1-naphthol and 3 thyl-N,N-diethylethylenediamine amino-1-diethylamino-2-propanol according to the meth 7-4-(3-dibenzofuranylazo)-1-naphthyl)-1,14-triethyidi od described in Example 8 herein for the synthesis of 1 ethylenetriamine (3-dimethylaminopropylamino)-naphthalene. 3-4-(3-piperidinopropylamino)-1-naphthylazol-2-diben 20 Alternatively, the desired azo compound can be pre zofuranol pared in the following manner: a solution of 12.9 g. (0.1 N-4-(3-dibenzofuranylazo)-1-naphthyl-N,N-diethyl-1, mole) of N,N-diethylepihydrinamine in 100 ml. of ethanol 4-pentanediamine is added with stirring to a solution of 24.8 g. (0.1 mole) 4-(3-dibenzofuranylazo)-N-1-(diethylaminoethyl)-cy of 3-(4-amino-1-naphthylazo)-pyridine in 200 ml. of clohexyl)-methyl-1-naphthylamine 25 ethanol and the mixture is boiled under reflux for 24 N-(2-bromoethyl)-4-(3-dibenzofuranylazo) - 1 - naph hours. The solvent is removed in vacuo and the residue thylamine, employed as a starting material in the above is purified as described above. The desired 1-diethyl procedure, is prepared as follows: a suspension of 18.3 g. amino-3-(4-(3-pyridylazo)-1-naphthylamino)-2-propanol (0.1 mole) of 3-aminodibenzofuran in 1 . of water con 30 trihydrochloride hydrate thus obtained melts at 153-155 taining 35 ml. (0.3 mole) of 48% aqueous hydrogen bro C. The intermediate 3-(4-amino-1-naphthylazo) - pyri mide is cooled to 0° C. and treated slowly with a solu dine, M.P. 185-187 C., is prepared from 1-naphthyl tion of 6.9 g. (0.1 mole) of sodium nitrite in 50 ml. of amine and diazotized 3-aminopyridine according to the water, maintaining the temperature at 0 to 5 C. The procedure described under Example 1 herein. resulting yellow suspension is stirred at 0° C. for one 35 1-diethylamino-3-(4-(3-pyridylazo)-1-naphthylamino half hour and is then poured with vigorous stirring into 2-propanol trihydrochloride can also be obtained by the a solution of 33.1 g. (0.1 mole) of N-(2-bromoethyl)-1- following procedure: a mixture of 37.7 g (0.1 mole) of naphthylamine, hydrobromide in 300 ml. of water. The 1-chloro-3-(4-(3-pyridylazo)-1-naphthylamino) - 2 - pro thick purple suspension thus obtained is stirred for 2 panol hydrochloride and 300 g. of diethylamine is placed hours at room temperature and the solid collected by 40 in a bomb and heated at 110° C. for 12 hours. The bomb filtration and dried in vacuo at 55° C. for 18 hours. The is allowed to cool, is carefully vented and the reaction mix hydrobromide salt is converted to the base by grinding ture poured into 2 1. of 10% aqueous sodium hydroxide with concentrated sodium hydroxide solution and acetone solution. This mixture is worked up as indicated above and the base is crystallized from chloroform. This is to give the desired 1-diethylamino-3-4-(3-pyridylazo)-1- the desired intermediate, N-(2-bromoethyl)-4-(3-dibenzo 45 naphthylamino)-2-propanol, trihydrochloride, monohy furanylazo)-1-naphthylamine, M.P. 157-158 C. drate, M.P. 155-157° C. The other intermediate 1-naphthylamines employed The intermediate 1-chloro-3-4-(3-pyridylazo)-1-naph herein can be prepared according to the procedures de thylamino-2-propanol, hydrochloride, is prepared by cou scribed under Examples 1 through 15. pling diazotized 3-aminopyridine into 1-chloro-3-(1-naph 50 thylamino)-2-propanol according to the procedure out Example 6 lined in Example 1 above for the preparation of 5-4-(2- To a solution of 9.3 g. (0.1 mole) of 3-aminopyridine diethylaminoethylamino)-1-naphthylazo-uracil. in 250 ml. of water and 35 ml. of concentrated hydro The following related compounds can be prepared us chloric acid is slowly added at 0° C. with stirring a solu ing similar methods, starting from the appropriate amino tion of 6.9 g. (0.1 mole) of sodium nitrite in 200 ml. 55 pyridine and 1-naphthylamine compounds: of water. Upon completion of the diazotization, the di 1-diethylamino-2-methyl-3-4-(3-pyridylazo)-1- azonium salt solution is added at 0 to 3' C. to a solu naphthylamino)-2-propanol, sulfate tion of 27.2 g. (0.1 mole) of 1-diethylamino-3-(1-naph 2-ethyl-(2-4-(3-pyridylazo)-1-naphthylamino thylamino)-2-propanol in 1 . of water containing 17 ml. ethyl)-amino-ethanol, diphosphate of concentrated hydrochloric acid and 300 ml. of 95% 60 5-4-(2-diethylaminoethylamino)-7-methoxy-1- ethanol. A deep red solution forms immediately. After naphthylazo)-2-phenoxypyridine, trihydrochloride 3 hours, the reaction mixture is made strongly alkaline 1-2-(2-[4-(3-pyridylazo)-1-naphthylamino]-ethoxy}- with sodium hydroxide solution and the organic layer ethyl-piperidine, salt with 4,4'-methylenebis 3-hy which separates is extracted with chloroform. The com droxy-2-naphthoic acid bined chloroform extracts are washed thoroughly with 65 3-(4-(2-bis(2-ethoxyethyl)-amino-ethylamino water and dried over anhydrous sodium sulfate. The dry 1-naphthylazopyridine, cholate ing agent is collected by filtration, the chloroform is 3-4-(2-diethylaminoethylamino)-7-phenyl-1- evaporated in vacuo, and the residue dissolved in ether naphthylazo)-pyridine, malonate and treated with anhydrous hydrogen chloride. The 4-4-(5-4-(2-diethylaminoethylamino)-1-naphthylazol purple hydrochloride which separates is collected by fil 70 2-pyridylamino butyl-morpholine tration and crystallized from an ethanol-ether mixture. 5-4-(2-dicyclohexylaminoethylamino)-1-naphthylazo After drying in vacuo for 48 hours at 40 C., the sample 2-picoline, disalicylate is allowed to equilibrate in the air. The red-brown solid The intermediate 1-naphthylamine compounds can be melts at 154-157 C, and is the desired 1-diethylamino 75 prepared according to the procedures outlined above to 3,189,421 17 18 gether with those described under Examples 1 through 15 4-(3-dimethylaminopropylamino)-1-naphthylazo - iso herein. quinoline, of formula, Example 7 5-aminobenzimidazole dihydrochloride (10.3 g., 0.05 mole) is diazotized and coupled into 13.5 g. (0.05 mole) 5 of 4-3-(1-naphthylamino)-propyl)-morpholine according to the procedure described under Example 1 herein. The desired 5-4-(3-morpholinopropylamino)-1-naphthylazo benzimidazole thus obtained, M.P. 220-223 C, has the formula, O NII (CII)3N O Y--/ M.P. 158-160° C. 5 Utilizing the preparative methods outlined under Ex N amples 1 through 15 herein, the following related com pounds can be prepared starting from the appropriate 1 NacN naphthylamine compound and amino or hydroxyisoquin oline: YN/ 4-4-(2-diethylaminoethylamino)-1-naphthylazo H isoquinoline Utilizing the preparative methods described under Ex 5-(4-(2-diethylaminoethylamino)-1-naphthylazo amples 1 through 15 herein, the following related com isoquinoline pounds can be prepared starting from the appropriate 1 25 7-(4-2,2-dimethyl-3-(1-pyrrollidinyl)-propylamino naphthylamine compound and amino or hydroxybenzimi 1-naphthylazo-3-ethylisocarbostyril dazole or indazole: 6-4-(2-diethylaminoethylamino)-1-naphthylazo 5 (or 6)-4-(2-diethylaminoethylamino)-1- isoquinoline naphthylazo-benzimidazole 8-3-(2,2-dimethylpiperidino)-propylamino-5-(6- 5-4-(2-diethylaminoethylamino)-1-naphthylazo 30 isoquinolylazo)-2-naphthoic acid 2-benzimidazolinethione 5-amino-8-4-(2-diethylaminoethylamino)-1- 5-4-(5-diethylamino-1-methylpentylamino)-1- naphthylazo isoquinoline naphthylazo-1H-indazole 1-(2-dimethylaminoethoxy)-3-ethyl-7-4-2- 5-(6-chloro-4-2-(ethylmethylamino)-ethylamino]- (isopropylmethylamino)-ethylamino-1-naphthylazo 1-naphthylazo-1,3-dimethyl-2-benzimidazolinone 35 isoquinoline 5 (or 6)-4-(2-4-(2-hydroxyethyl)-1-piperazinyl 4-4-5-(dimethylaminomethyl)-tetrahydrofur ethylamino-1-naphthylazo)-2-benzimidazolecar furylamino]-1-naphthylazo-isoquinoline boxylic acid 1-3-6-chloro-4-(7-isoquinolylazo)-1-naphthylamino o-methyl-O-4-(1-phenyl-5-benzimidazolylazo)-1-naph 2,2-dimethylpropyl-4-methylpiperazine: thylaminomethyl)-1-piperidine-ethanol 40 8-4-(2-diisopropylaminoethylamino)-1- 8-(5 (or 6)-benzimidazolylazo)-5-(2-diethylamino naphthylazol-5-isoquinolinol ethylamino)-2-naphthalenesulfonic acid 8-4-(2-diethylaminoethylamino)-1-naphthylazo 5-4-(3-dimethylamino-2-ethoxypropylamino)-1- 5-(3-diethylaminopropylamino)-isoquinoline naphthylazol-2-methyl-1H-naphth-1,2]-imidazole 4-4-(2-diethylaminoethylamino)-1-naphthylazo 7(or 4)-4-3-(diallylamino)-propylamino)-1- 45 3-hydroxy-2-methylisocarbostyril naphthylazo)-2-methyl - 5(or 6) - benzimidazolesulfonic acid The starting material, 1-(3 - dimethylaminopropyl 6(or 5)-4-(2-diethylaminoethylamino)-1- amino)-naphthalene, can be prepared as follows: a mix naphthylazo-2-methyl-5-benzimidazolol ture of 28.8 g. (0.2 mole) of 1-naphthol, 40.4 g (0.4 50 mole) of 3-dimethylaminopropylamine and 31.2 g (0.3 5 (or 6)-4-(2-ethyl (2-diisopropylaminoethyl)- mole) of sodium bisulfite in 250 ml. of water is shaken in amino-ethylamino-1-naphthylazo-benzimidazole a steel bomb at 150° C. for 8 hours. The mixture is 5 (or 6)-(4-2-(2-diethylaminoethoxy)-ethylamino rinsed from the bomb with water, made strongly alkaline 1-naphthylazo-benzimidazole with sodium hydroxide solution and extracted thoroughly The starting material, 4-3-(1-naphthylamino)-propyl 55 with ether. The ether extracts are dried over anhydrous morpholine, can be prepared as follows: a mixture of sodium sulfate, the ether removed in vacuo, and the residue 86.4 g. (0.6 mole) of 1-naphthol, 102.8 g. (0.714 mole) distilled in vacuo through a 6-inch Vigreux column to of 4-(1-aminopropyl)-morpholine, 93.6 g. (0.9 mole) of give the desired 1-(3-dimethylaminopropylamino)-naph Sodium bisulfite and 600 ml. of water is agitated in a pres thalene as a yellow oil, B.P. 184-185° C./2.5 mm., no Sure vessel at 150° C. for 8 hours. The reaction mixture 60 1,6054. is removed from the reactor and made alkaline with so The other intermediate 1-naphthylamine compounds dium hydroxide solution. The product is collected by are prepared according to the procedures described under filtration and crystallized from aqueous ethanol to give Examples 1 through 15 herein. the desired 4-3-(1-naphthylamino)-propyl-morpholine as colorless crystals, M.P. 82-83.5° C. 65 Example 9 The other intermediate 1-naphthylamine compounds N - (2-diethylaminoethyl)-N-(4-amino-1-naphthyl)-tri are prepared according to the procedures described under fluoroacetamide, monohydrochloride (9.75 g., 0.025 mole) Examples 1 through 15 herein. is diazotized according to the procedure described under Example 8 Example 2 herein. To this cold diazonium salt solution 70 is then added 100 g. of ice and a cold solution of 4.0 g. 5-aminoisoquinoline (14.4 g., 0.1 mole) is diazotized (0.027 mole) of 8-hydroxyquinoline in 100 ml. of water, and coupled with 22.8 g. (0.1 mole) of 1-(3-dimethyl 8.4 ml (0.050 mole) of 6 N aqueous sodium hydroxide aminopropylamino)-naphthalene according to the proce and 2.03 g (0.025 mole) of sodium acetate. A reddish dure outlined under Example 1 herein. Crystallization brown precipitate forms immediately giving a thick sus of the crude dye from 2-propanol gives the desired 5- 75 pension. The reaction mixture is stirred at 013 C. for 3,139,421 20 2 hours, and the intermediate trifluoroacetamide, of ing to the procedure described under Example 1 herein. formula, The red dye thus obtained is the desired 6-4-2-(2-diethyl aminoethylthio) - ethylamino - 1 - naphthylazo -2,3-di cific methylquinoxaline, of formula S (CH).N.C.H.), NH(CH)2S (CH)N(CHs),

0 N-N- -OH N N N a CH3 is collected by filtration, washed with water and dried in t NN/II. vacuo at 40 C. for 18 hours. The crude trifluoroacetam 15 Utilizing the preparative methods outlined under Ex ide is crystallized from 2-propanol, M.P. 158-160 C. amples 1 through 15 herein, the following related com The N-(2-diethylaminoethyl)-2,2,2-trifluoro-N-4-(8- pounds can be prepared starting from the appropriate 1 hydroxy-5-quinolylazo)-1-naphthyl)-acetamide (8.5 g.) is naphthylamine compound and aminoquinoxaline or ami suspended in 75 ml. of methanol and treated with 25 ml. noquinazoline: of a 2 N sodium hydroxide solution in methanol together 20 6 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazo with 5 ml. of water. After stirring at room temperature 2,3-dimethylquinoxaline for 44 hours, the residue is diluted with 150 ml, of water, 1 - {2 - 4 - (6 - methoxy-7-quinazolinylazo)-1-naphthyl excess Dry Ice is added, and the reaction mixture is con amino-ethyl-3-piperidinol centrated in vacuo to a volume of 150 ml. The red dye 6 - 4 - (2,2-dimethyl-3-piperidinopropylamino)-1-naphth that precipitates is the desired 5-4-(2-diethylaminoethyl 25 ylazo-quinoxaline amino)-1-naphthylazo)-8-quinolinol, of formula, 6 - {4 - 2 - (allylethylamino)-ethylamino-1-naphthyl azo)-quinazoline 5 - {4 - 2 - (cyclohexylmethylamino) - ethylamino - 1 naphthylazo)-7-methoxyquinoxaline 30 5 - {4 - {2 - 4 - (2 - piperidinoethyl)-piperidino-ethyl amino-1-naphthylazo-2,3-quinoxalinediol 6 - 4 - (2 - diethylaminoethylamino)-1-naphthylazo)-2,3- diphenylquinoxaline 7 - 4 - (2 - dimethylaminocyclohexylamino)-1-naphthyl 35 azo-quinazoline 6 - 4 - (2 - dimethylaminoethylamino)-1-naphthylazol-4- Crystallization from a dimethylformamide-water mixture ethyl-3,4-dihydro-2(1H)-quinoxaline gives reddish brown crystals, M.P. 161-163 C, 5 - {4 - 2 - bis(2 - diethylaminoethyl)-amino-ethylami By similar procedures, the following related compounds no-1-naphthylazo-quinazoline can be prepared, starting from the appropriate N-(dialkyl 40 5 - {4 - 2 - (hexahydro-1-azepinyl)-ethylamino]-1-naph aminoalkyl)-N-(4-amino-1-naphthyl)-trifluoroacetamide thylazo-7-methoxyquinoxaline and hydroxyquinoline via the N-(4-(quinolylazo)-1-naph a - (L4 - (2 - quinoxalinylazo)-1-naphthylamino]-methyl}- thyl) - N - (dialkylaminoalkylamino) - c,a,a-trifluoroace 1-piperidineethanol tamides: 45 N - 2 - (2 - diethylaminoethylthio)-ethyl)-1-naphthyla 5 - 4 - (3 - piperidinopropylamino) - 1 - naphthylazo)-6- mine, employed as a starting material in the above proced quinolinol ure, is prepared from 1-(2-bromoethylamino)-naphthalene 3 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazo and 2-diethylaminoethanethiol according to the following 2,4-quinolinediol method: 33.9 g (0.2 mole) of 2-diethylaminoethanethiol 7 - 4 - (3 - diethylaminopropylamino)-7-sulfo-1-naph 50 hydrochloride is suspended in ammonia and extracted with thylazol-8-hydroxy-5-quinolinesulfonic acid toluene. To this dried toluene solution is then added a 5 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazol Solution of 12 g. of sodium methoxide in 40 ml. of meth anol and the mixture is stirred at room temperature for aOSethyl-2-quinuclidinyl)-6-hydroxy-4-quinolinemeth 2 hours. A toluene solution of 1-(2-bromoethylamino)- 8 - hydroxy - 5 - {4-3-(2-morpholinoethylthio)-propyl 55 naphthalene, prepared by suspending 66.2 g (0.2 mole) of amino]-1-naphthylazo)-7-quinolinesulfonic acid the hydrobromide in concentrated ammonium hydroxide 5-4-(2-(cyclohexylmethylamino)-ethylamino-1-naph and extracting with toluene, is then added and the mixture thylazo)-4-methyl-2,6-quinolinediol boiled under reflux for 18 hours. Upon cooling, the so 5 - 4 - (2 - diethylaminoethylamino)-1-naphthylazol-7- dium bromide which separates is collected by filtration (dimethylaminomethyl)-8-quinolinol 60 and the filtrate is washed twice with water, dried over 5 chloro- 7 - 4-(4-diethylamino-1-methylbutylamino)- anhydrous potassium carbonate and evaporated in vacuo 1-naphthylazo-8-quinolinol on the steam bath. The residue is distilled in vacuo The intermediate N-(4-quinolylazo-1-naphthyl)-N-(di through an 8-inch Vigreux column to give the desired alkylaminoalkyl) - a,a,a-trifluoroacetamides are prepared N- I2 - (2 - diethylaminoethylthio) - ethyl)-1-naphthyla fromnoalkyl-N-(4-amino-1-naphthyl)-a,a,c-trifluoroacetam the appropriate hydroxyquinoline and N-dialkylami 65 Eas a yellow oil, B.P. 164-165 C/0.1 mm, 25 The other intermediate 1-naphthylamine compounds are ide compounds in accordance with the method described prepared according to the procedures described under Ex above for the preparation of N-(2-diethylaminoethyl)-2, amples 1 through 15 herein. yl)-acetamide.22- trifluoro-N-[4-(8-hydroxy-5-quinolylazo)-1-naphth. 70 Example 11 Example 10 A solution of 5.0 g (0.05 mole) of 2-aminothiazole in 5-amino-2,3-dimethylguinoxaline (17.3 g., 0.1 mole) is 250 ml. of 50% sulfuric acid is cooled to -10° C., and diazotized and coupled into 30.3 g (0.1 mole) of N-(2- nitrosyl sulfuric acid (3.5 g. of sodium nitrite in 35 ml. (2-diethylaminoethylthio)-ethyl)-1-naphthylamine accord 75 of concentrated sulfuric acid) is slowly added, keeping 3,189,421 21 22 the temperature between -10 and -5°C. The resulting naphthalene compounds employed herein are prepared ac light brown solution is stirred for 30 minutes, then added cording to the procedures described under Examples 1 to a solution of 12.7 g (0.05 mole) of 1-2-(1-naphthyl through 15. amino)-ethyl-piperidine in 250 ml. of 10% sulfuric acid. Example 12 A dark red solution formed. After stirring for 2 hours 3-aminoquinoline (14.4 g., 0.1 mole) is diazotized and at 0° to -10° C., 1 I. of water is added yielding a purple coupled into 24.2 g. (0.1 mole) of 1-(2-diethylamino solution. Stirring is continued for 1 hour and the mixture ethylamino)-naphthalene according to the procedure out is made alkaline with sodium hydroxide solution with lined under Example 1 herein for the preparation of 5 cooling. The mixture is stirred for 24 hours and the 4 - (2 - diethylaminoethylamino)-1-naphthylazol-uracil. sticky dye collected by filtration and washed with copious O Crystallization of the crude dye from 2-propanol (decolor amounts of water to remove inorganic salts. The product izing charcoal) gives the desired 3-[4-(2-diethylamino is dissolved in chloroform; the chloroform solution is ethylamino)-1-naphthylazo]-quinoline, of formula, washed well with water, dried over anhydrous potassium carbonate, and the solvent removed in vacuo. The vis cous residue is dissolved in acetone and precipitated by 15 pouring the acetone solution into water. Upon heating the suspension, a crystalline solid separates which is col lected by filtration and dried in vacuo at 45 C. Crystal lization from an ethanol-water mixture gives the desired 1-2-[4-(2-thiazolylazo)1 - naphthylamino-ethyl-piperi 20 -N- dine, of formula, NN NII (CII) N as red crystals, M.P. 124-125 C. s Alternatively, the desired 3-4-(2-diethylaminoethyl 25 amino)-1-naphthylazo-quinoline and other related com pounds can be prepared by alkylating the appropriate (4- amino-1-naphthylazo)-heterocyclic compound with a suit able dialkylaminoalkyl halide. Thus, 3-[4-(2-diethyl aminoethylamino)-1-naphthylazol-quinoline is prepared 30 according to the following procedure: to a xylene solution i N of 29.8 g. (0.1 mole) of 3-(4-amino-1-naphthylazo)-quino as emerald green, shimmering crystals, M.P. 135-137° C. line and 13.6 g. (0.1 mole) of 2-diethylaminoethylchloride Utilizing the preparative methods outlined under Exam is added 13.8 g. (0.1 mole) of anhydrous potassium car ples 1 through 15 herein, the following related compounds bonate and the resulting mixture is boiled under reflux for can be prepared starting from the appropriate 1-naphthyl 35 24 hours. The cooled reaction mixture is washed with 50% amine compound and aminothiazole: sodium hydroxide solution and the xylene layer is sepa 2-4-(2-diethylaminoethylamino)-1-naphthylazol rated and dried over anhydrous sodium sulfate. Volatile thiazole materials are removed in vacuo and the residue is crystal 2-4-2-(isopropylmethylamino)-ethylamino]-1- 40 lized from 2-propanol to give the desired 3-4-(2-diethyl naphthylazo)-5-nitrothiazole aminoethylamino)-1-naphthylazo)-quinoline as red crys 2-4-(2-(2-diethylaminoethyl)ethylaminol-ethylamino tals, M.P. 124-125 C. 1-naphthylazo-4-methylthiazole The intermediate 3-(4-amino-1-naphthylazo)-quinoline, 2-4-(6-diethylaminohexylamino)-1-naphthylazo M.P. 238-239 C., is prepared from diazotized 3-amino thiazole quinoline and 1-naphthylamine according to the procedure 2-4-(3-dimethylamino-2,2-dimethylpropylamino)-1- 45 described above for the coupling with 1-(2-diethylamino naphthylazo-)-4-phenylthiazole ethylamino)-naphthalene. 4-(2-dimethylaminoethyl)-1-(3-4-(2-thiazolylazo)-1- Utilizing the preparative methods described under Ex naphthylamino-propyl)-piperidine amples 1 through 15 herein, the following related com 2-[4-(2-diethylaminoethylamino)-1-naphthylazol-4- pounds can be prepared, starting from the appropriate 1 (trifluoromethyl)-thiazole 50 naphthylamine and aminoquinoline precursors: 2-4-(2-diethylaminoethylamino)-5-methoxy-1- 6-4-(2-diethylaminoethylamino)-1-naphthylazol naphthylazo-thiazole quinoline 2-[4-(2-diethylaminoethylamino)-1-naphthylazol-4- 1-2-[4-(3-quinolylazo)-1-naphthylamino-ethyl-3- ethylsulfonyl-5-nitrothiazole 55 piperidinol 2-4-(2-dihexylaminoethylamino)-1-naphthylazo 3-4-(2-diethylaminoethylamino)-7-methyl-1- thiazole naphthylazo-quinoline 2,2'-(2-[4-(2-thiazolylazo)-1-naphthylaminol 3-(4-(2-bis(3-diethylaminopropyl)aminol-ethylamino ethylimino-diethanol 1-naphthylazo-quinoline 1-methyl-4-2-4-(2-thiazolylazo)-1-naphthylamino 60 2-4-(2-diethylaminoethylamino)-1-naphthylazo ethyl)-piperazine quinoline The starting material, 1-2-(1-naphthylamino)-ethyl 3-(6-ethoxy-4-2-(isopropylmethylamino)-ethylamino piperidine, can be prepared as follows: a mixture of 19 g. 1-naphthylazo-quinoline (0.057 mole) of N-(2-bromoethyl)-1-naphthylamine, hy 3-(4-(6-diethylaminohexylamino)-1-naphthylazo drobromide and 100 ml. of piperidine is boiled under re 65 quinoline flux for 20 hours and cooled; 100 ml. of 10% sodium hy 3-(4-3-(hexahydro-1-azepinyl)-propylamino]-1- droxide solution is added, and the mixture extracted with naphthylazo-quinoline ether. The combined ether extracts are washed thorough 8-(2-diethylaminoethylamino)-5-(3-quinolylazo)-1- ly with water, dried over anhydrous potassium carbonate, naphthalenesulfonic acid and the ether removed on the steam bath. "The residue 70 3-(4-(2-(1-methyl-2-piperidinyl)-ethylamino]-1- is distilled in vacuo through an 8-inch Vigreux column naphthylazo-quinoline to give the desired 1-2-(1-naphthylamino)-ethyl)-piperi 3-(4-1-(diethylaminomethyl)-cyclohexylmethyll dine as a pale yellow oil with a purple fluorescence, B.P. amino-1-naphthylazo-quinoline 168-170/0.5 mm., n25 1.6088. 4-2-[4-(3-quinolylazo)-1-naphthylamino-ethyl)-1- The other intermediate 1-(dialkylaminoalkylamino)- 75 piperazineethanol 3,139,421 23 24 The other intermediate 1-naphthylamine compounds aminoethylchloride hydrochloride in accordance with the are prepared according to the procedures described under method set forth under Example 1 herein for the prep Examples 1 through 15 herein. aration of 1-(2-diethylaminoethylamino)-naphthalene. Example 13 The other intermediate 1-naphthylamine compounds can 4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one (10.2 5 be prepared according to the methods outlined under g., 0.05 mole) is diazotized and coupled into 12.8 g. (0.05 Examples 1 through 15 herein. mole) of 1-(2-diethylaminoethylamino)-6-methoxynaph Example 14 thalene according to the procedure outlined under Ex To a solution of 9.75 g. (0.025 mole) of N-(2-diethyl ample 6 herein for the preparation of 1-diethylamino O aminoethyl)-N-(4-amino - 1 - naphthyl)-trifluoroacetam 3-(4-(3-pyridylazo) - 1 - naphthylamino)-2-propanol, tri ide, monohydrochloride, in 100 ml. of ice water and 4.5 hydrochloride. Crystallization of the crude dye from a ml. of concentrated hydrochloric acid is added 25 ml. 2-propanol-methanol mixture gives the desired 4-4-(2- of 1 molar sodium nitrite solution over a period of 2 diethylaminoethylamino)-7-methoxy - 1 - naphthylazol minutes. The resulting red solution is stirred for 4 min 2,3-dimethyl-1-phenyl-3-pyrazolin-5-one, dihydrochloride, utes and added in one portion to a solution of 10.51 g. as blue crystals, of formula, 5 (0.025 mole) of 8-(2-diisobutylaminoethylamino)-6- methoxyquinoline, dihydrochloride, monohydrate, in 100 NH(CB).N.C.H.), ml. of water, 10 ml. of concentrated hydrochloric acid and 100 g. of ice. The maroon reaction mixture is stirred .2IICl 20 at 0-5 C. for 2 hours, 15 ml. of concentrated amonium CIO hydroxide is added and the maroon solid which sepa rates is collected by filtration and washed with water. Upon drying in vacuo, the crude intermediate trifluoro N-N- -- C it, acetamide of formula, N-CH3 y C F.CO-NCH).N.C.H.),

CHO 30 |- which in hydrated form melt at 200-202 C. NsN NH(CH)N(CHCH(CH3), Utilizing the preparative methods described under Ex N N amples 1 through 15 herein, the following related com 1 pounds can be prepared, starting from the appropriate 1-naphthylamine and pyrazole intermediates: melts at 50-70° C. The above amide (16.7 g.) is dissolved in 400 ml. of 3-(4-4-2-(allylethylamino)-ethylamino-1-naphthyl methanol, 15 ml. of 6 N aqueous sodium hydroxide is azo-3-methyl-5-oxo-2-pyrazolin-1-yl)-4-chloro added, and the mixture is stirred at 40 C. under nitrogen 4-4-2,2-dimethyl-3-(1-pyrrolidinyl)-propylamino]-1-benzenesulfonic acid, hydrochloride for 5 days. The mixture is cooled, and the deep maroon naphthylazo)-5-hydroxy-3-methyl-1-pyrazoleethanol, 40 crystals which separate are collected by filtration and dihydrochloride washed successively with cold methanol and water. Crys 4-4-(2-diethylaminoethylamino)-1-naphthylazo)-2,3- tallization from 95% ethanol gives the desired 5-4-(2- dimethyl-1-phenyl-3-pyrazolin-5-one diethylaminoethylamino) - 1 - naphthylazo) - 8 - (2-diiso 1-methyl-4-2-[4-(4-pyrazolylazo)-1-naphthylaminol butylaminoethylamino)-6-methoxyquinoline, of formula, ethyl)-homopiperazine 4-7-chloro-4-(4-diethylamino-1-methylbutylamino)-1- naphthylazol-3,5-dimethylpyrazole 4-(4-[2-(ethylmethylamino)-ethylamino]-1-naphthyl aZo-5-hydroxy-1-p-sulfophenyl-3-pyrazolecarboxylic acid 50 4-4-(3-dimethylamino-2,2-dimethylpropylamino)-1- N-N-( -NH(CII) NCHCH (CH3)] naphthylazo)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one 5-4-(3-diethylaminocyclohexylamino)-1-naphthylazol { NN 3,4-dimethyl-1-phenylpyrazole - 55 M.P. 92-94 C. (dec.). 4-4-(2-(2-ethoxyethyl) (2-hydroxyethyl)amino-ethyl By similar procedures, the following related com amino-1-naphthylazo)-5-hydroxy-1-p-sulfophenyl pounds can be prepared, starting from the appropriate 3-pyrazolecarboxylic acid N-(dialkylaminoalkyl)-N-(4 - amino-1-naphthyl)-trifluo 2,3-dimethyl-4-(4-(2-[4-(2-piperidinoethyl)piperidino roacetamide and aminoquinoline via the N-(4-(quinolyl ethylamino-1-naphthylazo-1-phenyl-3-pyrazolin-5- 60 aZo)-1-naphthyl) - N - (dialkylaminoalkylamino)-ox,a,c- m-(4-4-(2-diisopentylaminoethylamino)-1-naphthylOne trifluoroacetamides: azol-5-hydroxy-3-methyl-1-pyrazolyl-benzenesulfonic 2-8-(2-diisobutylaminoethylamino)-5-[4-(2-diisopropyl acid aminoethylamino)-1-naphthylazo]-6-quinolyloxy}- 3 (or 5)-4-(2-methyl(2-piperidinoethyl)amino-ethyl ethanol amino-1-naphthylazo)-4-pyrazolecarboxylic acid. 4-3-(5-[4-(2-diethylaminoethylamino)-1-naphthylazol 4-4-(3-diethylamino-2-hydroxypropylamino)-1-naph 6-methoxy-8-quinolylamino}-propyl)-1-piperazine thylazol-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one ethanol 8-(3-dimethlaminopropylamino)-4-(2,3-dimethyl-5-oxo 1-(2-6-methoxy-5-[4-(3-piperidinopropylamino)-1- 1-phenyl-3-pyrazolin-4-ylazo)-2-naphthalenesulfonic naphthylazol-8-quinolylamino)ethyl)-4-methyl 70 p1perazine acid 8-(4-amino-1-methylbutylamino)-5-[4-(2-diethylamino 1-(2- diethylaminoethylamino)-6-methoxynaphthalene, ethylamino)-1-naphthylazol-6-methoxyquinoline B.P. 195-196° C./2 mm., n25 1.5904, employed as a 5-[4-(2-diethylaminoethylamino)-1-naphthylazo)-8-(4- starting material for the above procedure, can be pre diethylamino-1-methylbutylamino)-6-methoxy pared from 6-methoxy-1-naphthylamine and 2-diethyl quinoline 3,139,421 25 26 5-4-(2-diethylaminoethylamino)-1-naphthylazo)-6- 5-7-chloro-4-(2-diethylaminoethylamino)-1-naph ethoxy-8-3-(1-piperazinyl)-propylaminol-quinoline thylazol-barbituric acid 6-methoxy-5-4-2-(4-methyl-1-piperazinyl)-ethyl 2,6-diamino-5-[4-(2-diethylaminoethylamino)-1- amino-1-naphthylazo-8-3-(4-methyl-1-piperazinyl)- naphthylazol-4-pyrimidinol propylamino)-quinoline 5-(4-2-(1-methyl-2-piperidyl)-ethylamino)-1- 6-methoxy-8-1-methyl-4-(4-methyl-1-piperazinyl)- naphthylazo-barbituric acid butylamino)-5-4-(2-(1-pyrrolidinyl)-ethylaminol 5-(4-2-(2-diethylaminoethoxy)-ethylamino)-1- 1-naphthylazo-quinoline naphthylazo-barbituric acid The intermediate N - (4-quinolylazo-1-naphthyl)-N- The intermediate N - 4 - (pyrimidylazo) - 1 - naph (dialkylaminoalkyl) - a,a,a - trifluoroacetamides are pre O thyl - N - (dialkylaminoalkylamino) - or,a,a - trifluoro pared from the appropriate aminoquinoline and N-dialkyl acetamides are prepared in a similar manner from the aminoalkyl-N-(4 - amino-1-naphthyl)-a,c,d-trifluoroacet appropriate pyrimidine and N-dialkylaminoalkyl-N-(4- amide compounds in accordance with the method de amino-1-naphthyl)-a,a,c-trifluoroacetamide compounds. scribed above for the preparation of N-(2-diethylamino ethyl)-N-(4-8-(2-diisobutylaminoethylamino) - 6-meth 15 Example 16 oxy-5-quinolylazo-1-naphthyl-2,2,2-trifluoroacetamide. A solution of 9.4 g (0.052 mole) of 6-amino-2H-1,4- benzothiazin-3 (4H)-one in 50 ml. of water, 50 ml. of Example 15 ethanol and 30 ml. of concentrated hydrochloric acid is N - (2 - diethylaminoethyl) - N - (4 - amino - 1 cooled to -5° C. and diazotized by the addition of 3.6 napthyl)-trifluoroacetamide, monohydrochloride (9.75 20 g. (0.052 mole) of sodium nitrite in 20 ml. of water. g., 0.025 mole), is diazotized according to the procedure After 5 minutes, the diazonium salt is added with stir described under Example 2 herein. To this cold diazo ring to a solution of 12.6 g. (0.052 mole) of 1-(2-diethyl nium salt solution is then added 400 g. of ice, followed aminoethylamino)-naphthalene in a mixture of 1 1. of by the slow addition of a warm solution of 3.2 g (0.025 water and 50 ml. of concentrated hydrochloric acid which mole) of barbituric acid in 4.2 ml. (0.025 mole) of 6 25 had previously been cooled to 0° C. The resulting N aqueous sodium hydroxide, 2.1 g (0.025 mole) of purple mixture is stirred for 2 hours, and the bright sodium bicarbonate and 200 ml. of water. The result orange-red base precipitated by the addition of an excess ing golden orange suspension is stirred for 1 hour at of concentrated ammonium hydroxide. The crude dye 0° C., a mixture of 25 ml. (0.025 mole) of 1 M so is collected by filtration and thoroughly triturated with dium bicarbonate and 4.2 ml. (0.025 mole) of 6 N 30 several portions of hot water. Crystallization from 2 aqueous sodium hydroxide is added, and the mixture propanol gives the desired 6-4-(2-diethylaminoethyl is allowed to warm slowly to room temperature. Stir amino) - 1 - naphthylazo - 2H - 14 - benzothiazin ring is continued for 48 hours and the brown gelatinous 3(4H)-one, of formula, precipitate is collected by filtration. This is resuspended NH(CH)N(CH), in water, stirred for 18 hours and treated with an excess of Dry Ice. The suspended solid is collected by filtra tion, washed with water and dried. Crystallization from an ethanol-dimethylformamide mixture gives the desired H 5 - 4 - (2 - diethylaminoethylamino) - 1 naphthylazol 40 N barbituric acid, of formula, NH(CH2)N(CH) rt Ns r as red luminous crystals, M.P. 213-214 C. In similar manner, the following related compounds O can be prepared by diazotizing the appropriate amino benzothiazine or aminophenothiazine and coupling the diazonium compounds thus obtained with the corre sponding 1-naphthylamine: 50 TNN 6-4-2-[4-(2-diethylaminoethyl)-piperidino-ethyl H amino-1-naphthylazo)-2H-1,4-benzothiazine 7-4-(2-diethylaminoethylamino)-1-naphthylazol-2- as reddish-black crystals, M.P. 209-213 C. By similar procedures, the following related compounds (trifluoromethyl)-phenothiazine can be prepared, starting from the appropriate 1-(dialkyl 5 5 6-4-(1-methyl-4-piperidylamino)-1-naphthylazol-2H aminoalkylamino)-naphthalene via the N-(4-(pyrimidyl 3-7-4-(2-diethylaminoethylamino)-1-naphthylazo)-6-1,4-benzothiazin-3 (4H)-one azo) - 1 - naphthyl) - N - (dialkylaminoalkylamino)- (2-dimethylaminoacetamido)-2-ethyl-3-methyl-2H o,a,c-trifluoroacetamides: 1,4-benzothiazin-4 (3H)-yl-1,2-propanediol 5-4-(2-diethylaminoethylamino)-1-naphthylazol-2- 60 6-7-chloro-4-(2-diethylaminoethylamino)-1-naph thiobarbituric acid thylazol-2H-1,4-benzothiazin-3 (4H)-one 5-(4-2-(isopropylmethylamino)-ethylamino]-1-naph 3-(4-(2-diethylamino-1-methylethylamino)-1-naph thylazo)-2-methyl-4,6-pyrimidinediol thylazo]-10-ethylphenothiazine 2-amino-5-(4-(2-bis(2-ethoxyethyl)-aminol-ethyl 7-[4-(2-diethylaminoethylamino)-1-naphthylazo)-6-(N- amino-1-naphthylazo)-4,6-pyrimidinediol 65 methylmethanesulfonamido)-2H-1,4-benzothiazine 5-4-(2-diethylaminoethylamino)-1-naphthylazo]-1,3- 4(3H)-ethanesulfonic acid, 1-oxide, monosodium dimethylbarbituric acid salt 6-amino-5-[4-(2,2-dimethyl-3-piperidinopropylamino)- 3-[4-(2-diethylaminoethylamino)-1-naphthylazo 1-naphthylazol-uracil phenothiazine 5-(4-3-4-(3-diethylaminopropyl)-1-piperazinyl-pro 70 10-(3-dimethylaminopropyl)-7-4-2-(isopropylmethyl pylamino)-1-naphthylazo)-barbituric acid amino)-ethylamino]-1-naphthylazo}-2-(trifluoro 1,3-diisopropyl-5-[4-(2-dimethylaminoethylamino)-1- methyl)-phenothiazine naphthylazol-barbituric acid 4-(2-[4-(3,4-dihydro-3-oxo-2H-1,4-benzothiazin-6- 2,6-diamino-5-[4-(3-diallylaminopropylamino)-1- ylazo)-1-naphthylamino-ethyl-1-piperazine naphthylazol-4-pyrimidinol 75 ethanol 3,189,421 27 28 10-ethyl-3-(4-2-(1-pyrrolidinyl)-ethylaminol-1- propriate 1-naphthylamine or 1-naphthol according to the 6-[4-(2-methyl-3-piperidinopropylamino)-1-naphthylnaphthylazo-phenothiazine, 5,5-dioxide procedures described under Examples 1 through 15. azol-2H-1,4-benzothiazin-3 (4H)-one Example 18 5-aminouracil (9.5 g., 0.075 mole) is diazotized and The other intermediate 1-(dialkylaminoalkylamino)- coupled into 21.3 g (0.075 mole) of 1-(5-diethylamino naphthalene intermediates are prepared according to the pentylamino)-naphthalene according to the procedure procedures described under Examples 1 through 15 outlined under Example 1 herein for the preparation of herein. 5- 4 - (2 - diethylaminoethylamino) - 1 - naphthylazol Example 17 uracil. Crystallization of the crude dye from a dimethyl 5-amino-8-quinolinol (10.0 g., 0.048 mole) is diazo O acetamide-water mixture gives the desired 5-4-(5-di tized and coupled into 12.4 g (0.048 mole) of 2-ethyl ethylaminopentylamino) - 1 - naphthylazo) - uracil, of 2 - (1 - naphthylamino)-ethyl)-amino-ethanol according formula, to the procdure outlined under Example 3 herein for the preparation of 5-4-(2-(2-diisopropylaminoethyl)-meth NHc H)N(CH) ylamino-1-naphthylazol-indazole. The crude dye base 5 is dissolved in 1 l. of ethanol, the solution is filtered, and the desired 2-ethyl{2 - 4 - (8-hydroxy-5-quinolyazo)-1- naphthylazol-ethyl}-amino-ethanol, dihydrochloride, of formula, 20 g-H. N-N N NH(CEI) NCHCHOH HO OH as deep red crystals, M.P. 170° C. (dec.). 25 Utilizing the preparative methods described under Ex amples 1 through 15 herein, the following related com pounds can be prepared, starting from the appropriate 1 (dialkylaminoalkylamino) - naphthalene and 5 - amino uracil: 30 5-4-(3-diethylamino-2-hydroxypropylamino-1-naph thylazo-uracil, salt with /2 formula weight 4,4'- methylenebis(3-hydroxy-2-naphthoic acid) is caused to precipitate by the addition of 50 ml. of 4 N 8-(2-diethylaminoethylamino)-5-(2,4-dihydroxy-5- ethanolic hydrogen chloride. The salt is collected by pyrimidinylazo)-2-naphthalenesulfonic acid filtration, dried in vacuo, and allowed to equilibrate in the 35 5-(4-(2-ethyl (2-hydroxyethyl)-aminol-ethylamino air. The brown hydrated solid melts at 190-192 C. 1-naphthylazo-uracil, cholate Utilizing the preparative methods outlined under Ex 5-(4-1-(diethylaminomethyl)-cyclohexylmethyl]- amples 1 through 15 herein, the following related com amino-1-naphthylazo-uracil, 8-chlorotheophyllinate pounds can be prepared starting from the appropriate 1 5-4-(8-diethylaminooctylamino)-1-naphthylazol naphthylamine compound and aminoquinoline: 40 uracil, phosphate 3-4-2-(5-ethyl-2-methylpiperidino)-ethylamino)-1- 5-4-(2-diethylaminoethylamino)-6-ethoxy-1-naph naphthylazo-quinoline thylazol-uracil, malonate 8-4-(2-diethylaminoethylamino)-1-naphthylazol-or 5-(4-2-(3-diethylaminopropylthio)-ethylamino)-1- (diethylaminomethyl)-2-phenyl-4-quinolinemethanol naphthylazo-uracil, succinate 5-(4-(2-bis(2-methoxyethyl)-amino-ethylamino-1- 5-(4-2,2-dimethyl-3-(1-pyrrolidinyl)-propylamino naphthylazo-quinoline 1-naphthylazo-uracil, B-resorcylate 3-4-(2-diethylaminoethylamino)-5-nitro-1-naph 5-4-(2-diethylaminoethylamino)-7-nitro-1-naph thylazo-quinoline thylazol-uracil, citrate 1-2-[4-(8-quinolylazo)-1-naphthylamino-ethyl)-1- 5-(4-2-(decahydro-1-quinolyl)-ethylamino]-1-naph azaspiro-4,5decane 50 thylazo-uracil, salt with 4-biphenylcarboxylic acid 2,2'-(3-5-phenylazo-8-quinolylazo)-1-naphthyl 5-4-2-(4-methyl-1-piperazinyl)-ethylamino]-1-naph amino-propylamino diethanol thylazo-uracil, adipate 2-8-4-(3-diethylamino-2-ethoxypropylamino)-1- 5-4-(2-dihexylaminoethylamino)-1-naphthylazol naphthylazo]-6-quinolyloxyethanol uracil, salicylate 3-(4-(2-(allylethylamino)-ethylamino]-1-naphthyl 55 5-(4-(2-(1-azaspiro[4,5ldecan-1-yl)-ethylamino azo-quinoline 1-naphthylazo-uracil, salt with 3-hydroxy-2-naph 8-{4-(5-(dimethylaminomethyl) tetrahydrofurfuryl thoic acid amino]-1-naphthylazo)-5-nitroquinoline 1 - (5 - diethylaminopentylamino) - naphthalene, B.P. 3-(4-2-(4-methyl-1-homopiperazinyl)-ethylamino 60 198-200 C./1.8 mm., n.5 1.5740, employed as a start 1-naphthylazo-quinoline ing material for the above procedure, can be prepared 6-4-(3-diethylamino-2-methylpropylamino)-7-meth from 1-naphthylamine and 5. diethylaminopentylchloride oxy-1-naphthylazol-5,8-diethoxy-4-methylcarbo hydrochloride in accordance with the methodset forth styril under Example 1 herein for the preparation of 1-(2-di 8-I4-(2-diethylamino-2-methylpropylamino)-1-naph 65 ethylaminoethylamino)-naphthalene. Other intermedi thylazol-quinoline ate 1-(dialkylaminoalkylamino)-naphthalenes can be pre 2-ethyl 2-(1-naphthylamino)-ethyl)-amino - ethanol, pared from a 1-naphthylamine or 1-naphthol compound B.P. 170-172 C./0.2 mm., n25 1.6109, employed as a according to the procedures outlined in Examples 1 starting material in the above procedure, is prepared from through 15 herein. N-(2-bromoethyl)-1-naphthylamine, hydrobromide and 70 Example 19 N-ethylethanolamine according to the method described 3-aminopyridine (9.3 g., 0.1 mole) is diazotized and under Example 5 herein for the preparation of 1,1-diiso coupled into 24.2g. (0.1 mole) of 1-(2-diethylamino propyl-4-methyl-7-(1-naphthyl)-diethylenetriamine. The ethylamino)-naphthalene according to the procedure out other intermediate 1 - (dialkylaminoalkylamino) - naph lined under Example 6 herein for the preparation of 1-di thalenes employed herein can be prepared from the ap ethylamino-3-(4-(3-pyridylazo) - 1 - naphthylamino-2- 3,139,421 29 30 propanol, trihydrochloride. The maroon solid thus ob ing related compounds can be prepared, starting from the tained, M.P. 139-141 C., is the desired 3-[4-(2-diethyl appropriately substituted 1-naphthylamine compound and aminoethylamino) - 1 - naphthylazol-pyridine, trihydro hydroxy or amino dibenzothiophene or thiaraphthene: chloride, of formula, 3-4-(2-diethylaminoethylamino)-1-naphthylazol NH(CII)N(CIs). 5 dibenzothiophene 5-4-(2-diethylaminoethylamino)-6-methoxy-1- naphthylazo-thianaphthene 3EICl 3-(4-2,3-bis(diethylamino)propylamino)-1-naphthyl azo-dibenzothiophene, 5-oxide O 1-2-[4-(4-amino-7-thianaphthenylazo)-1-naphthyl N-cN aminol-ethyl)-1-azaspiro[4.5 decane 2-[4-(4-diethylaminopentylamino)-1-naphthylazol N/ 5-(4-2-(hexahydro-2-methyl-1-pyridazinyl)-ethylaminoldibenzothiophene, 5,5-dioxide containing 3% moles of water of hydration. 15 1-naphthylazo)-2-thianaphthenecarboxylic acid Utilizing the preparative methods described under Ex 2-4-(2-methyl(1-methyl-4-piperidyl)-aminol-ethyl amples 1 through 15 herein, the following related com amino-1-naphthylazo-3-thianaphthen-3-ol pounds can be prepared, starting from the appropriate 1 5-(4-2-[2-(2-dimethylaminoethoxy)-ethoxyl-ethyl naphthylamine and aminopyridine precursors: amino-1-naphthylazo-thianaphthene 2-4-(2-diethylaminoethylamino)-1-naphthylazo 20 5-(4-2-(2-diethylaminoethyl)-cyclopentylaminol-1- pyridine, trihydrochloride naphthylazo-thianaphthene, 1,1-dioxide 4-(2-diethylaminoethyl)-1-(2-4-(3-pyridylazo)-1- 1-2-4-(1-bromo-4-dibenzothiophenylazo)-1-naphthyl naphthylamino-ethyl-piperidine amino-ethyl-piperidine 4-4-(2-diethylaminoethylamino)-1-naphthylazo N'-[4-(6-amino-7-thianaphthenylazo)-1-naphthyl)-N- pyridine, trihydrochloride 25 ethyl-N-hexyl-1,3-propanediamine 3-4-(4-diethylamino-1-methylbutylamino)-1-naphthyl 1-2-[4-(8-ethoxy-2-dibenzothiophenylazo)-1-naphthyl azol-pyridine amino)ethyl-4-ethylpiperazine 3-4-(3-diethylaminocyclohexylamino)-1-naphthylazol pyridine The starting material, N-butyl-N-methyl-N'-1-naphthyl 3-4-(6-diethylaminohexylamino)-1-naphthylazo 30 enediamine, B.P. 142-144 C./0.1 mm., n25 1.5800, is pyridine prepared from 1-naphthylamine and 2-(butylmethyl 3-4-(3-diethylamino-2,2-dimethylpropylamino)-1- amino)-ethyl chloride, hydrochloride, according to the naphthylazo-pyridine procedure outlined under Example 1 for the preparation 1-5-[4-(3-pyridylazo)-1-naphthylamino)-pentyl)- of 1 - (2 - diethylaminoethylamino) - naphthalene. The piperidine 35 other substituted 1-naphthylamines employed are pre 3-4-(2-dimethylamino-1-methylethylamino)-1- pared according to procedures similar to those outlined naphthylazo-pyridine under Examples 1 through 15. 3-4-2-[2-(2-diethylaminoethoxy)ethyl-ethylamino}- Example 21 ethylamino-1-naphthylazo-pyridine 40 5-aminouracil (6.4 g., 0.05 mole) is diazotized and 3-4-2-(isopropylmethylamino)-ethylamino)-1- coupled into 15.7 g (0.05 mole) of 1,14-triethyl-7-(1- naphthylazo-pyridine naphthyl)-diethylenetriamine according to the procedure 3-4-2-(hexahydro-4-methyl-1,4-diazepin-1-yl)-ethyl outlined under Example 4 herein for the preparation of amino]-1-naphthylazo-pyridine 8 - 4 - (3 - diethylamino - 2,2-dimethylpropylamino)- The other substituted 1-naphthylamines employed here 1-naphthylazol-5,6-dimethoxyquinoline, trihydrochloride. in are prepared according to procedures similar to those Crystallization of the crude dye from a methanol-2-propa described under Examples 1 through 15. nol mixture gives the desired 5-4-(2-(2-diethylamino ethyl) - ethylamino - ethylamino} - 1 - naphthylazo}- Example 20 uracil, trihydrochloride, of formula, 2-aminodibenzothiophene (4.7 g., 0.024 mole) is di azotized and coupled into 6.1 g (0.024 mole) of N-butyl 50 N-methyl-N'-1-naphthylethylenediamine according to the procedure described under Example 1 herein. The crude red dye is washed thoroughly with cold water, dissolved in a hot methanol-acetone mixture, and poured with stir ring into water containing a few drops of ammonium hy droxide. The finely divided precipitate thus obtained is coagulated by heating, collected by filtration, and crys tallized from 2-propanol. This is the desired N-butyl N'-(4 - (dibenzothiophene - 2 - ylazo) - 1 - naphthyl]- N-methylethylenediamine, of formula, 60 (H, as dark blue crystals, M.P. 164-167 C. NH (CH)N(CH2)3CH Utilizing the preparative methods described under Ex amples 1 through 15 herein, the following related com 65 pounds can be prepared, starting from the appropriate 1 naphthylamine and pyrimidine intermediates: 4,6-diamino-5-[4-(2-diethylaminoethylamino)-1- N-N- naphthylazol-pyrimidine 70 2,4-diamino-5-[4-(2-diethylaminoethylamino)-1- naphthylazo]-6-ethylpyrimidine NS/ 2,4-bis(diethylamino)-5-[4-(1-methyl-3-piperidylmethyl M.P. 120-121 C. amino)-1-naphthylazopyrimidine Utilizing preparative procedures similar to those de 2,4-diamino-5-4-(2-(isopropylmethylamino)-ethyl Scribed under Examples 1 through 15 herein, the follow 75 aminol-1-naphthylazo)-pyrimidine 3,139,421 31 32 2-amino-5-7-chloro-4-(2-diethylaminoethylamino)-1- 3-amino-7-4-(2-diethylaminoethylamino)-1-naphthyl naphthylazol-4-piperidinopyrimidine azol-2,8-dimethyl-5-phenylphenazinium chloride, 2,4,6-triamino-5-4-2-(4-methyl-1-piperazinyl)-ethyl hydrochloride amino]-1-naphthylazo-pyrimidine 5-(4-(2-(2-hydroxyethyl)methylamino-ethylamino 4-amino-5-[4-(2-diethylaminoethylamino)-1-naphthyl 5 1-naphthylazo)-1,4-phthalazinediol azol-2-(4-piperidinobutylamino)-pyrimidine 6-4-(2-diethylaminoethylamino)-1-naphthylazol 2-(2-diethylaminoethylamino)-5-[4-(2-diethylamino 1,4-benzog phthalazine ethylamino)-1-naphthylazol-4-methoxy 5-4-(4-diethylamino-1-methylbutylamino)- pyrimidine 1-naphthylazo. 1,4-dimethoxyphthalazine 4-diethylamino-5-4-(2-(isopropylmethylamino)-ethyl 10 2-4-(3-diethylamino-2,2-dimethylpropylamino)- amino]-1-naphthylazo)-2-(5-piperidinopentylamino)- 1-naphthylazol-8-dimethylamino-3-methyl phenazine pyrimidine 2,3-dihydro-2-methyl-5-4-2-(1-methyl-2-piperidyl)- 4-diethylamino-2-(4-diethylaminobutylamino)-5-[4-(2- ethylamino]-1-naphthylazo-1,4-phthalazinedione diethylaminoethylamino)-1-naphthylazol-pyrimidine 7-4-3-(4-ethyl-1-piperazinyl)-propylamino)-1- 2-amino-4-anilino-5-[4-(2-diethylaminoethylamino)-1- naphthylazo-2-phenazinol naphthylazol-pyrimidine 5 5-(4-(4-(diethylaminomethyl)-cyclohexylmethylaminol 4-amino-2-(4-diethylamino-1-methylbutylamino)-5-4- 1-naphthylazo-2,3-dihydro-1,4-phthalazinedione (4-diethylamino-1-methylbutylamino)-1-naphthylazol 7-4-(3-diisopropylaminopropylamino)-6-methoxy-1- 6-methylpyrimidine naphthylazol-5-phenyl-3 (5H)-phenazinone 2,4-bis(3-piperidinopropylamino)-5-[4-(3-piperidino 20 3-4-2-(2-dimethylaminoethylthio)-ethylamino propylamino)-1-naphthylazol-pyrimidine 1-naphthylazo)-5-methylphenazinium chloride 1,14 triethyl - 7 - (1 - naphthyl)-diethylenetriamine, The intermediate 1-(dialkylaminoalkylamino)-naphtha B.P., 145-148 C./0.1 mm., n25 15715, employed as a lenes employed herein are prepared from 1-naphthylamine starting material in the above procedure, is prepared from or 1-naphthol according to the procedures described under N-(2-bromoethyl)-1-naphthylamine, hydrobromide and 25 Examples 1 through 15. N,N,N'-triethylethylenediamine according to the method described under Example 3 herein for the preparation of Example 23 1,1- diisopropyl - 4 - methyl-7- (1 - naphthyl) - diethyl 5-amino-8-methylguinoline (5.3 g., 0.03 mole) is di enetiamine. The other intermediate 1-(dialkylamino azotized and coupled into 7.6 g. (0.03 mole) of 4-(2- alkylamino)-naphthalenes employed herein can be pre 30 diethylaminoethyl)-1-(2-(1-naphthylamino)-ethyl-piperi pared from the appropriate naphthalene compound ac dine according to the procedure outlined under Example 6 cording to the procedures described under Examples 1 herein for the preparation of 1-diethylamino-3-4-(3-py through 15. ridylazo)-1-naphthylamino)-2-propanol, trihydrochloride. Example 22 Crystallization of the crude dye from a mixture of 2 5-amino-1,4-dihydroxyphthalazine (17.7 g., 0.1 mole 35 propanol and methanol gives the desired 5-(4-2-[4-(2- is diazotized and coupled into 24.3 g (0.1 mole) of diethylaminoethyl)-piperidino)-ethylamino-1 - naphthyl 1-(2- diethylaminoethylamino)-naphthalene according to azo-8-methylquinoline, trihydrochloride, of formula, the procedure outlined under Example 3 herein for the preparation of 5-4-(2-((2-diisopropylaminoethyl)-meth NH(CH)N X-CHCHN (CH) ylamino)-1-naphthylazoj}-indazole. Crystallization of 40 the crude dye from a dimethylacetamide-2-propanol mix ture gives the desired 5-[4-(2-diethylaminoethylamino)-1- naphthylazol-1,4-phthalazinediol, of formula,

NH(CH2)2N (CEI)

as a deep purple solid, M.P. 145-147 C. 50 Utilizing the preparative methods described under Hs-N- Examples 1 through 15 herein, the following related com pounds can be prepared, starting from the appro HO OH priate substituted 1-naphthylamine and aminoquinoline N-N compound: 55 6-4-3-(4-methyl-1-piperazinyl)-2,2-dimethylpropyl as greenish-black crystals, M.P. 211-213° C. amino]-1-naphthylazo-quinoline Utilizing the preparative methods described under 3-4-(3-dimethylamino-2-methylpropylamino)-6-methyl Examples 1 through 15 herein, the following related com 1-naphthylazo-quinoline 60 3-4-(4-diethylamino-2-isopropyl-1-methylbutylamino)- pounds can be prepared, starting from the appropriate 1-naphthylazo-quinoline 1-naphthylamine and aminophthalazine or aminophena 5-4-(3-diethylaminopropylamino)-1-naphthylazol Zine precursors: 7-piperidinomethyl-8-quinolinol 5-(4-(2- 2-(2-piperidinoethyl)-piperilino)-ethylamino 1-naphthylazo)-1,4-phthalazinediol 8-(4-2-hydroxy-3-(methylpropylamino)-propylaminol 2-[4-(2-diethylaminoethylamino)-1-naphthylazol 65 1-naphthylazo-6-quinolinol phenazine 5-(2-diethylaminoethylamin)-8-(3-quinolylazo)-2- 6-(6-chloro-4-(2-(1-pyrrolidinyl)-ethylamino]-1- naphthoic acid naphthylazo-1,2,3,4-tetrahydro-2,3-dimethyl 1-2-[4-(3-quinolylazo)-1-naphthylaminol-ethyl)- 1,4-phthalazinedione 3-piperidinemethanol 70 6-ethoxy-5-methoxy-8-}4-[2-(2-piperidinoethoxy)- 3-diethylamino-7-[4-(2-diethylaminoethylamino)- ethylamino]-1-naphthylazo-quinoline 1-naphthylazol-5-phenylphenazinium chloride, 3-4-(2-(4-dimethylaminopiperidino)-ethylamino hydrochloride 1-naphthylazo)-quinoline 6-4-2-(ethyl(2-piperidinoethyl)-aminol-ethylamino 5-(2-diethylaminoethylamino)-8-(5,6-dimethoxy-8- 1-naphthylazo-1,4-phthalazinediol 75 quinolylazo)-2-naphthol 3,189,421 33 34 8-4-4-diethylaminomethyl)-cyclohexylmethylamino mide. The intermediate N-(3-bromopropyl)-1-naphthyl 1-naphthylazo-5-methoxyquinoline amine, hydrobromide, thus obtained melts at 152-154 C. 4-4-2-(cyclopentylmethylamino)-ethylamino-1- This compound is subsequently allowed to react with naphthylazo-quinoline piperidine according to the procedure described under 4-(2-diethylaminoethyl)-1-(2-(1-naphthylamino)-ethyl]- 5 Example 3 herein for the preparation of 1,1-diisopropyl piperidine, B.P. 208-209 C./0.2 mm., n25 1.5795, em 4-methyl-7-(1-naphthyl)-diethylenetriamine to give the ployed as a starting material in the above procedure, is pre desired intermediate, 1-3-(1-naphthylamino)-propyl pared from N-(2-bromoethyl)-1-naphthylamine, hydro piperidine, as off white crystals, M.P. 70-72 C. bromide and 4-(2-diethylaminoethyl)-piperidine according The other intermediate 1-(dialkylaminoalkylamino)- to the method outlined under Example 3 herein for the O naphthalenes employed herein can be prepared from the preparation of 1-1-diisopropyl-4-methyl-7-(1-naphthyl)- appropriate 1-naphthylamine or 1-naphthol according to diethylenetriamine. The other substituted 1-naphthyl the procedures described under Examples 1 through 15. amine intermediates employed herein can be prepared Example 25 from the appropriate 1-naphthylamine or 1-naphthol com 5-aminobenzotriazole (13.4 g., 0.1 mole) is diazotized pound according to the procedures described under Ex 5 and coupled into 22.8 g. (0.1 mole) of N,N-dimethyl amples 1 through 15. N2-1-naphthyl-1,2-propanediamine according to the pro Example 24 cedure outlined under Example 3 herein for the prepara 3-aminopyridine (4.7 g., 0.05 mole) is diazotized and tion of 5 - {4 - {2 - (2-diisopropylaminoethyl)-methyla coupled into 13.4 g. (0.05 mole) of 1-3-(1-naphthyl 20 mino-1-naphthylazo-indazole. Crystallization of the amino)-propyl-piperidine according to the procedure out crude dye from ethanol gives the desired 6-4-(2-dimeth lined under Example 3 herein for the preparation of ylamino - 1 - methylethylamino)-1-naphthylazol-1H-ben 5-(4-(2-(2-diisopropylaminoethyl)-methylamino - ethyl zotriazole, of formula, amino)-1-naphthylazo-indazole. Crystallization of the CH crude dye from 2-propanol gives the desired 1-3-4-(3- 25 NHCHCH.N(CH), pyridylazo) - 1 - naphthylamino-propyl - piperidine, of formula, NH(CH2)3N { 30 N-N- -NH as orange-red crystals, M.P. 197-199 C. Utilizing the preparative methods described under Ex 35 amples 1 through 15 herein, the following related com pounds can be prepared, starting from the appropriate el substituted 1-naphthylamine and aminotriazole, amino benzotriazole, or aminotetrazole precursors: as maroon crystals, M.P. 130-123 C, 40 64-(2-diethylaminoethylamino)-1-naphthylazo)-1H Utilizing the preparative methods described under Ex benzotriazole amples 1 through 15 herein, the following related com 6-amino-7-4-(2-diethylaminoethylamino)-1-naphthyl pounds can be prepared, starting from the appropriate azo-H-benzotriazole Substituted 1-naphthylamine and aminopyridine: 5-(4-(2-4-(2-morpholinoethyl)-piperidino-ethylamino 5-4-(2-diethylaminoethylamino)-1-naphthylazol-2- 1-naphthylazo-1H-benzotriazole methoxypyridine. 4-4-(3-dimethylaminopropylamino)-6-phenyl-1-naph 2-chloro-5-[4-(2-diethylaminoethylamino)-1-naph thylazol-1-methyl-1H-benzotriazole thylazo-pyridine. 4-amino-7-4-2-diethylamino-1-(methoxymethyl)- decahydro-1-(2-4-(3-pyridylazo)-1-naphthylaminol ethylamino-1-naphthylazo 1H-benzotriazole ethyl-quinoline. 1-2-[4-(s-triazol-3-ylazo)-1-naphthylamino-ethyl-4- 4-5-[4-(2-morpholinoethylamino)-1-naphthylazo-2- 50 piperidinol pyridyl-morpholine. 4-4-(3-dimethylaminopropylamino)-5-sulfo-1-naphthyl 3-(4-(2-((2-2-dimethylaminoethyl)-methylamino azol-1H-benzotriazole-1-acetic acid ethyl-methylamino-ethylamino)-1-naphthylazo 5-(4-2,2-dimethyl-3-(1-pyrrollidinyl)-propylamino)-1- pyridine. naphthylazo-s-triazole-3-carboxylic acid. 1-methyl-2-(2-4-(3-pyridylazo)-1-napthylamino-ethyl 55 5-4-(2-diethylaminoethylamino)-1-naphthylazo)-1H piperidine. tetrazole 3-(4-(5-(diethylaminomethyl)-tetrahydrofurfurylaminol 6-4-3-bis(3-diethylaminopropyl)-aminol-propyl 1-naphthylazopyridine. amino-1-naphthylazo)-1H-benzotriazole 3-5-chloro-4-(2-diethylaminoethylamino)-1-naphthyl 60 3-4-(2-diethylaminoethylamino)-1-naphthylazol azol-pyridine. s-triazole 3-4-(2-diethylaminoethylamino)-6-ethoxy-1-naphthyl 5-6-chloro-4-(2-diethylaminoethylamino)-1-naphthyl aZo-pyridine. azol-1-methyl-1H-tetrazole 1-2-[4-(3-pyridylazo)-1-naphthylamino]-ethyl)-1- 5-amino-4-4-(2-diethylaminoethylamino)-1-naphthyl azaspiro4.5 decane. azol-6-methyl-2-phenyl-2H-benzotriazole 3-4-(2-dimethylaminoethylamino)-1-naphthylazol 65 3-6-chloro-4-(2-diethylaminoethylamino)-1-naphthyl pyridine, trihydrochloride. azol-5-imino-1-phenyl-A2-1,2,4-triazoline 2-(2-4-(2-methyl-5-pyridylazo)-1-naphthylamino 6-(4-5-(isopropylmethylamino)-pentylamino-1- ethyl-pentylamino-ethanol, trihydrochloride. naphthylazo-5-hydroxy-1H-benzotriazole-4- 1-3-(1-naphthylamine)-propyl)-piperidine, employed 70 carboxylic acid as a starting material in the above procedure, is prepared 1-((2-4-(1H-benzotriazol-5-ylazo)-1-naphthylamino as follows: N-(3-hydroxypropyl)-1-naphthylamine is al ethyl-ethylamino-2-methyl-2-propanol lowed to react with hydrobromic acid according to the N,N-dimethyl- N2 - 1-naphthyl-1,2-propanediamine, method outlined under Example 3 herein for the prepara B.P. 118-120' C./0.2 mm., employed as a starting mate tion of N-(2-bromoethyl)-1-naphthylamine, hydrobro 75 rial in the above procedure, is prepared from 1-naphthyl 3,139,421 35 36 amine and 2-dimethylamino-1-methylethylchloride hydro Example 27 chloride in accordance with the method set forth under N - (2 - diethylaminoethyl)-N-(4-amino - 1 - naph Example 1 herein for the preparation of 1-(2-diethyl thyl)-trifluoroacetamide, monohydrochloride (19.5 g., aminoethylamino)-naphthalene. 0.05 mole) is diazotized at 0° C. according to the pro The other intermediate 1-(dialkylaminoalkylamino)- cedure described under Example 14 herein. Subse naphthalenes employed herein can be prepared from the quently, a solution of 8.7 g., 0.05 mole) of 3-methyl-1- appropriate 1-naphthol or 1-naphthylamine precursors phenyl-5-pyrazolone in 200 ml. of water, 8.4 ml. of 6 N according to the procedures described under Examples 1 sodium hydroxide, and 4.2 g of sodium bicarbonate is through 15. slowly added at 0-5° C. to the diazonium salt solution, Example 26 O 4.2 g of sodium bicarbonate is added, and the mixture 2,4-dimethoxy-5-aminopyrimidine (15.5 g., 0.09 mole) stirred at room temperature for 18 hours. The orange is diazotized and coupled into 24.3 g (0.09 mole) of N,N- precipitate is collected by filtration, washed with water, diisopropyl-N'-1-naphthylethylenediamine according to dried, and crystallized from acetone. The intermediate procedure described under Example 1 herein. The red N.- (2 - diethylaminoethyl) - 2,2,2 - trifluoro - N - 4-(3- crystalline dye that separates in the desired 5-4-(2-diiso 5 methyl - 5 - oxo - 1 - phenyl - 2 - pyrazolin - 4 - ylazo)- propylaminoethylamino) - 1-naphthylazol-2,4-dimethoxy 1 - naphthyl) - acetamide thus obtained, of formula, pyrimidine, of formula, g NHCH).NICICI).). 20 Fic N(CH).N.C.H.),

N 25 H.

CHO- N Jo CH N-N- - Toti, - N Crystallization of the crude dye from acetone gives red TNN/ needles, M.P. 157-158 C. 30 In like manner, the following related compounds can be prepared, starting from equivalent quantities of the appropriate aminopyrimidine and 1-(dialkylaminoalkyl amino)-naphthalene compounds: 5-[4-(2-diethylaminoethylamino)-1-naphthylazol-2,4- 35 melts at 154-155 C. dimethoxypyrimidine, salt with (5,6,7,8-tetrahydro-1- A portion of the above amide (10 g.) is dissolved in methyl-2-naphthyloxy) acetic acid 800 ml. of acetone. Water (10 ml.) and 30 ml. (0.06 2,4-diethoxy-5-4-2-4-2-(4-methyl-1-piperazinyl)- mole) of 2 N sodium hydroxide solution are added, and ethyl-piperidino-ethylamino)-1-naphthylazo the resulting mixture is stirred for 20 hours at room tem pyrimidine 40 perature. The mixture is filtered, and the filtrate evapo 1-4-(2,4-diphenoxy-5-pyrimidinylazo)-1-naphthyl rated to dryness in vacuo. The residue is extracted with aminol-3-dipropylamino-2-propanol, pyromellitate ether and the combined ether extracts are washed suc 5-(4-2-(isopropylmethylamino)-ethylamino)-1- cessively with dilute ammonium hydroxide and saturated naphthylazo)-2,4-dimethylpyrimidine, salt with 1,5- Sodium chloride solution and dried over anhydrous mag naphthalenedisulfonic acid nesium sulfate. The ether solution is evaporated until 5-6-bromo-4-(2-diethylaminoethylamino)-1-naphthyl crystallization begins, and the product is collected by fil azo)-2-methylpyrimidine tration. Crystallization from 2-propanol gives the desired 5-(4-2-(2-diisopropylaminoethyl)-methylamino 4 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazo) ethylamino-1-naphthylazo)-2,4-dimethoxypyrimidine, 3 - methyl- 1 - phenyl - 2 - pyrazolin - 5 - one, of formula, hydrochloride 50 1-(2-4-(2,4-dimethoxy-5-pyrimidinylazo)-1-naphthyl NHCH) 2N (C2H5) amino-ethyl)-3-piperidinol 5-(4-2-(cyclopentylmethylamino)-ethylamino]-1- naphthylazo)-4,6-dimethoxy-2-methylpyrimidine 5-(4-5-(dimethylaminomethyl)-tetrahydrofurfuryl 55 amino]-1-naphthylazo)-4-methoxy-2-methyl N-N- CI pyrimidine, terephthalate - 3 5-[4-(4-diethylamino-1-methylbutylamino)-1- -- N naphthylazol-2,4-dimethoxypyrimidine, sulfate TNN/ 4-chloro-5-4-(2-diethylamino-1-(diethylaminoethyl)- 60 ethylamino]-1-naphthylazo)-6-methoxy-2- methylpyrimidine 2,4-dimethoxy-5-(4-(2-(tetrahydro-1-azepinyl)-ethyl aminol-1-naphthylazo-pyrimidine 65 as brown iridescent needles, M.P. 154-155° C. The starting material, N,N-diisopropyl-N'-1-naphthyl By similar procedures, the following related com ethylene diamine, is obtained as a yellow oil, B.P. 178 pounds can be prepared, starting from the appropriate 179 C./0.9 mm., n25 1.57.82, by the condensation of N. (dialkylaminoalkyl) - N - (4-amino - 1 - naphthyl)- 1-naphthylamine and 2-diisopropylaminoethylchloride, trifluoroacetamide and pyrazole compound via the N-4- hydrochloride according to the procedure outlined under 70 (pyrazolylazo) - 1 naphthyll - N - (dialkylaminoalkyl Example 1 herein for the preparation of 1-(2-diethyl amino) - a,a,a - trifluoroacetamide precursors: aminoethylamino)-naphthalene. 1-3-4-( 3,5-diamino-1-phenyl-4-pyrazolylazo)-1- The other intermediate 1-(dialkylaminoalkylamino)- naphthylaminol-propyl)-piperidine. naphthalenes employed herein can be prepared according 3,5-diamino-4-(4-[2-(isopropylmethylamino)-ethyl to the procedures described under Examples 1 through 15, 75 aminol-7-chloro-1-naphthylazo}-pyrazole. 3,139,421 37 38 3,5-diamino-4-4-(2-diethylaminoethylamino)-1- C./0.4 mm., n25 1.5990. This intermediate can be naphthylazo)-1-methylpyrazole. prepared from 1 - naphthylamine and 2 - (methylethyl 3,5-diamino-4-4-(3-diethylamino-2,2-dimethyl amino)-ethylchloride, hydrochloride according to the pro propylamino)-1-naphthylazo-1-phenylpyrazole. cedure described under Example 1 herein for the prepara 3,5-diamino-4-(4-(2-diethylaminoethylamino)- 5 tion of 1-(2- diethylaminoethylamino)-naphthaline. The 6-methoxy-1-naphthylazol-1-methylpyrazole. other substituted 1-naphthylamines employed herein are 3,5-diamino-4-4-2-bis(2-ethoxyethyl)-amino prepared according to procedures similar to those de ethylamino-1-naphthylazo-pyrazole. scribed under Examples 1 through 15. 3,5-diamino-4-4-(2-diethylaminoethylamino)- 1-naphthylazo)-1-phenylpyrazole. Example 29 1-3-4-(3,5-diamino-4-pyrazolylazo)-1-naphthyl O A solution of 11.7 g. (0.03 mole) of N-(2-diethylamino amino-propyl-piperidine. ethyl)-N-(4-amino-1-naphthyl)-trifluoroacetamide, mono 1-anilino-4-(4-(2-diethylaminoethylamino)-1- hydrochloride, is diazotized according to the procedure naphthylazol-5-oxo-2-pyrazoline-3-carboxylic acid. described in Example 2 herein and coupled into a solu 4-4-(5-diethylaminopentylamino)-1-naphthylazol tion of 7.0 g (0.03 mole) of N-(2-diethylaminoethyl)- 1,3-diphenyl-5-pyrazol. 1,2,3,4-tetrahydroquinoline in 15 ml. of concentrated hy p-4-4-(2-diethylaminoethylamino)-1-naphthylazo drochloric acid, 100 ml. of water and 150 g. of ice. After 5-hydroxy-3-methyl-1-pyrazolyl)benzenesulfonamide. stirring for 2 hours at 0-5° C., 19.5 ml. of concentrated 4-4-3-4-(2-dimethylaminoethyl)-piperidino-propyl ammonium hydroxide and 100 ml. of water are added amino-1-naphthylazo-5-oxo-1-phenyl-2-pyrazoline 20 and the precipitate that separates is extracted with ether. 3-carboxylic acid. The combined ether extracts are washed with water and then with saturated sodium chloride solution and dried The intermediate N-4-pyrazolylazo-1-naphthyl)-N- over anhydrous magnesium sulfate. The ether is re (dialkylaminoalkyl) - or,a,a - trifluoroacetamides are pre moved in vacuo, and the intermediate trifluoroacetamide pared from the appropriate pyrazole compound and N-di is dissolved in 300 ml. of ethanol and is stirred with 30 ml. alkylaminoalkyl - N - (4 - amino - 1 - naphthyl) - or,a,c- (0.060 mole) of 2 N sodium hydroxide in methanol and trifluoroacetamide in accordance with the methods de 30 ml. of water under nitrogen at room temperature for scribed under Examples 2, 9, 14, and 29 herein. 24 hours. The mixture is treated with excess Dry Ice and Example 28 500 ml. of water and concentrated in vacuo to 500 ml. The red supernatant is decanted from the sticky red dye 7-aminobenzofauinoline (7.8 g., 0.04 mole) is diazo 30 which separates and the dye is treated with 250 ml. of tized and coupled into 9.1 g (0.04 mole) of N-ethyl-N- 2-propanol and 12 ml. (0.024 mole) of a 2 N 2-propanol methyl-N'-1-naphthylethylenediamine according to the hydrogen chloride mixture. One liter of anhydrous ether procedure described under Example 3 herein. Crystalliza is then added slowly with stirring, depositing a red dye tion of the red dye thus obtained from boiling 2-propanol which crystallizes after 4 hours. Recrystallization from gives the desired 7-4-2 - (ethylmethylamino) - ethyl a methanol-ethyl acetate mixture gives the desired 1 amino-1-naphthylazo-benzof guinoline, of formula, (2-diethylaminoethyl)-6-4-(2- diethylaminoethylamino)- (I, 1-naphthylazol-1,2,3,4-tetrahydroquinoline, dihydrochlo NH(CH)2NCIIs ride, of formula, 40 NHCI).N(C.I).

2EEC 45 N ( . ) NN as maroon crystals, M.P. 182-184 C. O (II) N(CH)2 Utilizing procedures similar to those described under M.P. 195-1985 C. Examples 1 through 15 herein, the following related com In like manner, the following related compounds can pounds can be prepared, starting from an appropriately be prepared, starting from the appropriate 1-(dialkyl substituted 1-naphthylamine and hydroxy or amino benzo aminoalkyl)-N-(4-amino-1-naphthy) - trifluoroacetamide quinoline or phenanthridine compound. and 1,2,3,4-tetrahydroquinoline, indoline, 1,2,3,4-tetra 4-2-1-(2-4-(7-benzofauinolinylazo) - 1 - naphthyl hydro-1,3-quinazoline, 3,4-dihydro-2H-1,4-benzoxazine, 2, amino-ethyl-4-piperidinyl-ethyl-1-piperazineethanol 3-dihydro-1H-naphth 2,1)-p-oxazine, 1,2,3,4-tetrahydro 10-4-2-(ethylpropylamino)-ethylamino-6-methoxy - 1 quinoxaline, or 1,2,3,4-tetrahydrobenzohquinoline via naphthylazo-6-methylphenanthridine the N-4 - (heterocyclicazo-1-naphthyl-N-(dialkylamino 8-4-(2-diethylaminoethylamino)-1-naphthylazo - benzo 60 alkylamino)-ox,a,c-trifluoroacetamides: fguinoline 6-4-(2-diethylaminoethylamino)-1-naphthylazol-2,3 - di 5-4-3-(3-diethylaminopropyl) - ethylamino - propyl hydro-1H-naphth 2, 1)-p-oxazine, hydrochloride amino-1-naphthylazo-benzo figuinoline 6-4-(2-diethylaminoethylamino)-1-naphthylazo - 1,2,3, 6-4-(4-diethylaminocyclohexylamino)-1 naphthylazol 4-tetrahydroquinoline, hydrochloride 4-methylbenzohquinolin-2(1H)-one 5-I4-(2-diethylaminoethylamino)-1-naphthylazo - indo 3-4-(2-diethylaminoethylamino) - 1 - naphthylazo] - 2 line, hydrochloride methylbenzohquinolin-4-ol 7-4-(2-diethylaminoethylamino)-1-naphthylazo-3,4-di 2-(2-diethylaminoethylamino)-1-(4-3- (isopropylmethyl hydro-2H-1,4-benzoxazine, hydrochloride amino)-propylaminol-7-methyl - 1 - naphthylazo - 6 70 6-4-(3-piperidinopropylamino)-1-naphthylazo-3,4 - di methylphenanthridine hydro-1 (2H)-quinolineethanol, hydrochloride 5-(2-diethylaminoethylamino)-6 - (4 - diethylaminoethyl 5-(4-2-(isopropylmethylamino)-ethylamino - 1 - naph amino-1-naphthylazo)-benzof guinoline thylazo-1-methylindoline, hydrochloride The starting material, N-ethyl-N-methyl-N'-1-naphthyl 1-(2-ethoxyethyl)-1,2,3,4-tetrahydro-6-4-(2 - piperidino ethylenediamine, is a viscous yellow oil, B.P. 146-147 75 ethylamino)-1-naphthylazo)-quinoline, hydrochloride 3,139,421 39 s 40 6-4-(2-diethylaminoethylamino)-1-naphthylazol - 1,2,3, 8-4-(4-diethylamino-1,2-dimethylbutylamino)-1-naph 4-tetrahydro-1,3-quinazolinediethanol, hydrochloride thylazo]-10H-1)-benzothiapyrano.3.2-cpyridin-10 5-I4-(2-diethylaminoethylamino)-7-methoxy - 1 - naph Oc thylazol-2-methylindoline, hydrochloride 6-4-3-(3-diethylaminopropylthio)-propylamino]-1- 5-chloro-1-(2-diethylaminoethyl)-8-4 - (2-diethylamino naphthylazo)-4,9-thiophanthrenedione. ethylamino)-1-naphthylazo) - 1,2,3,4 - tetrahydro - 6 7-4-(2-diethylaminoethylamino)-1-naphthylazol-2,3- methylguinoline, hydrochloride dihydro-2,6-dimethyl-1H-pyrrolo[3,4-c]pyridine. 3-6-4-(2-diethylaminoethylamino)-1-naphthylazo]-1,2, 3-diethylamino-7-4-3-(3-diethylaminopropyoxy)-prop 3,4-tetrahydro-2,7-dimethyl-1-quinolyl-1,2 - propane pylamino]-1-naphthylazo-2-methylphenazoxonium diol, hydrochloride chloride. 5-6-chloro-4-(3 - diethylamino - 2,2 - dimethylpropyl 0. 9-4-(2-diethylaminoethylamino)-1-naphthylazo amino)-1-naphthylazol-1-(2- diethylaminoethyl) - indo pyrido 1,2-albenzimidazol-8-ol. line, hydrochloride N,N,N',N'-tetramethyl-2-(1-naphthylamino)-1,3 - pro 6-4-(2-diethylaminoethylamino)-1-naphthylazo) - 1,2,3, panediamine, B.P. 137-138 C./0.3 mm., n25 1.5836, em 4-tetrahydroquinoxaline, hydrochloride 15 ployed as a starting material in the above preparation, is 6-4-(2-diethylaminoethylamino)-1-naphthylazo) - 1,2,3, prepared from 1-naphthol and 1,3,-bis(dimethylamino)-2- 4-tetrahydrobenzohquinoline, hydrochloride propylamine according to the procedure outline under 6-4-2-(hexahydro - 1 - azepinylethylamino - 1 - naph Example 8 herein for the preparation of 1-(3-dimethyl thylazo-1,2,3,4-tetrahydrolepidine, hydrochloride aminopropylamino)-napthalene. The other intermediate 6-4-(2-diethylaminoethylamino)-1-naphthylazo - 1,2,3, 20 1-naphylthylamines employed herein can be prepared from 4-tetrahydro-1,4-dimethylquinoxaline, hydrochloride the appropriate 1-naphthol or 1-naphthylamine precursors The other N-4-(heterocyclicazo)-1-naphthyl-N-(di according to the procedure described under Examples 1 alkyaminoalkylamino)-a,a,c-trifluoroacetamides are pre through 15. pared in a similar manner from the appropriate amino heterocyclic compounds and N-dialkylaminoalkyl-N-(4- 25 Example 31 amino-1-naphthyl)-ox,a,c-trifluoroacetamides. 5-amino-2-butoxypyridine (16.6 g., 0.1 mole) is di azotized and coupled into 24.2 g (0.1 mole) of 1-(2-di Example 30 ethylaminoethylamino)-naphthalene according to the 3-amino-10-ethylphenothiazine, 5,5-dioxide (0.85 g., procedure described under Example 3 herein for prepara 0.0031 mole) is diazotized and coupled into 0.84 g. 30 tion of 5 - {4-{2-((2-diisopropylaminoethyl)-methyl (0.0031 mole of N,N,N',N'-tetramethyl-2-(1-naphthyl aminol-ethylamino-1-naphthylazo, -inadzole. Crystal amino)-1,3-propanediamine according to the procedure lization of the crude dye from ethanol gives the desired 2 outlined under Example 6 herein for the preparation of 1 butoxy - 5 - 4 - (2 - diethylaminoethylamino) - 1 - naph diethylamino - 3 - 4 - (3 - pyridylazo) - 1 - naphthyl thylazol-pyridine, of formula, amino)-2-propanol, trihydrochloride. Purification of the 35 crude dye from a mixture of acetone, ether, and ethanolic hydrogen chloride gives the desired 3-4-(2-dimethyl amino - 1 - (dimethylaminomethyl) - ethylamino - 1 naphthylazo)-10-ethylphenothiazine, 5,5-dioxide, trihy drochloride, of formula, 40 CHN(CH3) NHCHCEIN(CH3) gill. as orange-red crystals, M.P. 92-94 C. Utilizing the preparative methods described under Ex amples 1 through 15 herein, the following related com pounds can be prepared, starting from the appropriate sub stituted 1-naphthylamine and aminopyridine or hydroxy OCOYs6, 50 pyridine compound: 3-(4-2-(1-propyl-2-pyrrolidinyl)-ethylamino-1-naph as a purple-brown hydrated solid, M.P. 195-197° C. thylazopyridine. Utilizing the preparative methods outlined under Exam 2-benzyloxy-5-4-(2-diisopentylaminoethylamino)-1- ples 1 through 15 herein, the following related compounds naphthylazo-pyridine. can be prepared, starting from the appropriate substituted 5-6-chloro-4-(2-diethylaminoethylamino)-1-naph 1-naphthylamine and hydroxy or aminoheterocyclic com thylazol-2-propoxypyridine. pound: 3-(4-2-(2,5-dimethyl-1-pyrrolidinyl)-ethylamino]-1- 2-4-(2-diethylaminoethylamino)-1-naphthylazol naphthylazo-pyridine. dibenzo Ib,f) (1,4,5)-thiadiazepine, 11,11-dioxide. 60 3-(4-(2-(2-diethylaminoethylthio)-ethylamino]-1- 3-hydroxy-2-4-2-(isopropylmethylamino)-ethylaminol napthylazo-pyridine. 1-naphthylazo-phenazoxonium hydroxide, inner salt. 8-(2-diethylaminoethylamino-5-(3-pyridylazo)-2- 7-4-3-diethylamino-1-(2-diethylaminoethyl)-propyl naphthalenesulfonic acid. amino]-1-naphthylazo)-5H-1lbenzothiapyrano (2,3- 1-methyl-4-2-[4-(3-pyridylazo)-1-naphthylamino cpyridin-5-one. 65 ethyl-piperazine. 8-4-(2-2-[2-(1-pyrrolidinyl)-ethyl-piperidino 5-I4-(8-diethylaminooctylamino)-1-naphthylazol-2- cthylamino-1-naphthylazo)-4.9-thiophanthrenedione. dimethylaminopyridine. 8-(2-diethylaminoethylamino)-5-(10-oxo-10H-1 ben 3-4-(2-dihexylaminoethylamino)-1-naphthylazol zothiapyrano3,2-b-pyridin-8-ylazo)-1-naphthoic acid. pyridine. 3-4-2-diethylaminoethyl)-cyclopentylaminol-1-naph 8-(6-ametamido-3-pyridylazo)-5-(2-diethylaminoethyl thylazo-7-dimethylamino-phenazathionium chloride. amino)-2-naphthoic acid. 3-imino-7-4-2-[4-(1-methyl-4-piperidyl)-piperidino 3-(4-1-(diethylaminomethyl)-cyclohexylmethylamino ethylamino-1-naphthylazo-3H-isophenoxazine. 1-naphthylazopyridine. 8-4-(2-diethylaminoethylamino)-5-ethoxy-1-naph 5-(2-diethylaminoethylamino)-8-(6-methoxy-3-pyridyl thylazo)-10H-1)-benzothiapyrano (3,2-bipyridine. 75 azo)-2-naphthol. 3,139,421 41 42 The other intermediate 1-(dialkylaminoalkylamino)- ture at -10 to 0° C. After the addition is complete, naphthalenes employed herein can be prepared from the stirring is continued for one-half hour at -10 to -5°C. appropriate 1-naphthol or 1-inaphthylamine precursors ac Subsequently, this diazonium salt mixture is added slowly cording to the procedures described under Examples 1 with stirring to a solution of 8.97 g (0.034 mole) of 1-(2- through 15. 5 (1-naphthylamino)-ethyl)-hexahydroazepine in 200 ml. of Example 32 enthanol. Stirring is continued at -10 to 0° C. for 3 8-aminoquinoline (5.8 g., 0.04 mole) is diazotized and hours, the reaction mixture is diluted to a volume of 2 l. coupled into 10.8 g. (0.04 mole) of 1-2-(1-naphthyl with water, and sufficient sodium hydroxide solution is amino)-ethyl-4-piperidino according to the procedure de added to make the mixture strongly alkaline. The mix scribed under Example 3 herein for the preparation of O ture is extracted with several portions of chloroform and 5 - 4 - 2 - (2 - diisopropylaminoethyl) - methylamino the combined chloroform extracts are dried and concen ethylamino)-1-naphthylazo)-indazole. Crystallization of trated on the steam bath. The viscous residue is washed the crude dye from acetonitrile gives the desired 1-2-[4- successively with several portions of petroleum ether (8 - quinolylazo) - 1 - naphthylaminoj - ethyl)- 4-piperi (B.P. 30-60° C.) and hot water and is crystallized from dinol, of formula, an acetonitrile-water mixture. The blue-green crystals thus obtained, M.P. 150-153 C., are the desired 2{4-2- NH(CH2)N X-OH (hexahydro-1-azepinyl)- ethylamino]-1-naphthylazo)-ben zothiazole, of formula, 20

N-N-(/ ) N N as red crystals, M.P. 168.5° C. (dec.). N Utilizing the preparative methods described under Ex amples 1 through 15 herein, the following related com pounds can be prepared, starting from the appropriate 30 f s/ aminoquinoline and substituted 1-naphthylamine Utilizing the preparative methods outlined under Ex precursors: amples 1 through 15 herein, the following related com 8-(2-diethylaminoethylamino)-5-4-(2-diethylamino pounds can be prepared, starting from the appropriate ethylamino)-1-naphthylazol-quinoline. Substituted 1-naphthylamine and aminobenzothiazole, 3-4-2-[2-(2-diethylaminoethyl)-piperidinol-ethyl aminobenzoxazole, aminonaphthothiazole, or amino amino-1-naphthylazo-quinoline. naphthooxazole: 3-4-2-(4-methyl-1-piperazinyl)-ethylamino]-1-naph 2-[4-(2-diethylaminoethylamino)-1-naphthylazo thylazo-quinoline. benzothiazole. 7-6-bromo-4-3-(1-pyrrolidinyl)-propylamino)-1- 2-4-2-ethylmethylamino)-ethylamino)-1- naphthylazo-quinoline. 40 naphthylazo-naphtho1,2thiazole. 7-4-2-[4-(2-diethylaminoethyl)-1-piperazinyl 2-(2-4-(6-ethoxy-2-benzothiazolylazo)-1- ethylamino-1-naphthylazo-8-hydroxy-5-quinolinesul naphthylamino-ethyl-ethylamino-ethanol. fonic acid. 5-I4-(2-diisopropylaminoethylamino)-5-methyl-1- 1-2-[4-(6-chloro-2-benzothiazolylazo)-1- naphthylazo]-6-methylquinoline. naphthylamino-ethyl-3-piperidinol. 8-amino-5-[4-(2-diethylaminoethylamino)-1- 2-4-2(2-diethylaminoethoxy)-ethylamino]-1- naphthylazo-quinoline. naphthylazo-naphthto[1,2]oxazole. 3-4-3-((tetrahydrofurfuryl)-methylaminol-propyl 2-[4-(2-diethylaminoethylamino)-7-methoxy-1- amino-1-naphthylazo-quinoline. naphthylazo]-benzoxazole. 3-(4-(6-piperidinohexylamino)-1-naphthylazol-quinoline. 50 2-4-(2-bis(3-diethylaminoproply)-amino-ethylamino 8-2-(isopropylmethylamino)-ethylamino)-5-(3- 1-naphthylazo-6-ethylsulfonylbenzothiazole. quinolylazo)-2-naphthol. 2-[4-(2-diethylaminopropylamino)-1-naphthylazo)-6- 5-amino-6-4-(2-diethylaminoethylamino)-1- ethoxybenzoxazole. naphthylazo-quinoline. 2-[4-(2-diethylaminoethylamino)-1-naphthylazo-N- 6-4-(2,3-dipiperidinopropylamino)-1-naphthylazol methyl-6-benzothiazolesulfonamide. quinoline. 2-4-(2-(1-pyrrolidinyl)-ethylamino]-1-naphthylazo)-6-benzothiazolepropanol. 1-2-(1-naphthylamino)-ethyl]-4-piperidinol, M.P. 104 2-4-(2-diethylaminoethylamino)-1-naphthylazo 106 C., employed as a starting material in the above pro 6,7,8,9-tetrahydro-naphtho2,1thiazole. cedure, is prepared from N-(2-bromoethyl)-1-naphthyl 60 6-acetamido-2(4-(3-diethylamino-2-methylpropylamino)- amine, hydrobromide and 4-piperidinol according to the 1-naphthylazo-benzothiazole. method described under Example 3 herein for the prepara 1-2-(1 - naphthylamino) - ethyl - hexahydroazepine, tion of 1,1-diisopropyl-4-methyl-7-(1-naphthyl)-diethyl B.P. 164-166 C./0.1 mm., n25 1.6062, employed as a enetriamine. The other intermediate 1-(dialkylaminoal starting material in the above preparation, is prepared kylamino)-naphthalenes enployed herein can be prepared 65 from N-(2-chloroethyl)-hexahydroazepine, hydrochloride from the apppropriate naphthalene compound according and 1-naphthylamine according to the procedure given to the procedure described under Examples 1 through 15. under Example 1 herein for the preparation of 1-(2-di Example 33 ethylaminoethylamino)-naphthalene. The other inter A solution of 5.03 g (0.034 mole) of 2-aminobenzothia 70 mediate 1-naphthylamines employed herein can be pre zole in 10 ml. of formic acid is added slowly at approxi pared from the appropriate 1-naphthol or 1-naphthyl mately 10 C. to a mixture of 40 ml. of sulfuric acid and amine precursors according to the procedures described 35 ml. of water. This mixture is cooled to -5° C. and under Examples 1 through 15. to it is added a solution of 2.31 g. (0.034 mole) of sodium Example 34 nitrite in 20 ml. of water while maintaining the tempera 75 3-amino-9-ethylcarbazole (21.0 g., 0.1 mole) is diazo 3,189,421 43 44 tized and coupled into 28.4 g. (0.1 mole) of N,N-diethyl The other intermediate 1-naphthylamine compounds N4-1-naphthyl-1,4-pentanediannine according to the pro are prepared according to the procedures described under cedure described under Example 1 herein. The maroon Examples 1 through 15 herein. dye thus obtained is the desired 3-(4-(4-diethylamino-1- methylbutylamino)-1-naphthylazol-9-ethylcarbazole, of Example 35 formula, 8-aminoquinoline (14.4 g., 0.1 mole) is diazotized and coupled into 24.2 g. (0.1 mole) of 1-(2-diethylamino ethylamino)-naphthalene according to the procedure de (H, scribed under Example 6 herein for the preparation of NHCH (CEI)N(CH) 1 - diethylamino - 3 - 4 - (3 - pyridylazo) - 1 - naphthyl 0 aminol-2-propanol, trihydrochloride. Crystallization of the crude dye from 2-propanol containing a few drops of a hydrogen chloride-2-propanol mixture gives the desired 8 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazo)- Ooh) 15 quinoline, dihydrochloride, of formula Utilizing the preparative methods outlined under Ex amples 1 through 15 herein, the following related com NH(CH)N(CH) pounds can be prepared, starting from the properly sub 20 stituted 1-naphthylamine and appropriate carbazole, in dole, oxindole, or pyrrole compound: 3-4-(2-diethylaminoethylamino)-1-naphthylazol-9- ethylcarbazole. 25 3-4-(2-diethylaminoethylamino)-7-methoxy-1- naphthylazol-9-ethylcarbazole. 6-4-(2-diethylaminoethylamino)-1-naphthylazo 1,2,3,4-tetrahydrocarbazole. 9-(2-diethylaminoethyl)-3-4-(2-diethylaminoethyl 30 amino)-1-naphthylazol-carbazole. as a purple-green solid, M.P. 156-158 C., containing 6-4-(3-diethylamino-2,2-dimethylproplyamino)-1- 3/2 moles of water. naphthylazo)-oxindole. Utilizing the preparative methods described under Ex 6-4-(3-piperidinopropylamino)-1-naphthylazol-1,2,3,4- amples 1 through 15 herein, the following related come tetrahydrocarbazole. pounds can be prepared, starting from the appropriate 2-4-2-morpholinoethylamino)-1-naphthylazol-carbazole. substituted 1-naphthylamine and aminoquinoline com 2-4-(2-diethylaminoethylamino)-1-naphthylazo pound: pyrrole. 3-(4-2-3-(1-methyl-2-pyrrolidinyl)piperidino 4-4-2-(isopropylmethylamino)-ethylamino]-1- ethylamino-1-naphthylazo-quinoline. . naphthylazo-3,5-dimethylpyrrole-2-carboxylic acid. 40 3-I-5-chloro-4-(2-diethylaminoethylamino)-1- 2-ethyl{2-[4-(9-ethyl-3-carbazolylazo)-1- naphthylazol-quinoline. naphthylamino-ethyl-amino-ethanol. 3-(4-2-(4-methoxypiperidino)-ethylamino)-1- 1-2-[4-(2-pyrrolylazo)-1-naphthylamino-ethyl naphthylazo-quinoline. pyrrollidine. 6-4-(2-diisobutylaminoethylamino)-1-naphthilyazo 1-(2-4-(2-methyl-5-indolylazo)-1-naphthylamino 2-(2-morpholinoethylamino)-lepidine. ethyl-4-methylpiperazine. 3-(4-2-(2,6-dimethylmorpholino)-ethylaminol-1- 9-ethyl-3-(4-(2-((2-diisopropylaminoethyl)- naphthylazo-quinoline. methylamino-ethylamino-1-naphthylazo-carbazole. 3-4-(2-diethylaminoethylamino)-6-phenyl-1- 7-4-(5-diethylaminopentylamino)-1-naphthylazol-2- naphthylazol-quinoline. indolecarboxylic acid. 50 3-4-2-bis-(2-methylally)-amino-ethylamino-1- 3-amino-6-4-(2-diethylaminoethylamino)-1- naphthylazo-quinoline. naphthylazol-carbazole. 8-4-2-decahydro-1-quinolyl)-ethylamino)-1- 7-4-(2-hydroxy-3-piperidinopropylamino)-1- naphthylazo-6-methoxyquinoline. naphthylazol-2-carbazolesulfonic acid. 6-amino-5-4-(2-diethylaminoethylamino)-1- N,N-diethyl-N4-1-naphthyl-1,4-pentanediamine, em 55 naphthylazo-quinoline. ployed as a starting material in the above procedure, is 3-7-ethoxy-4-(2-(3-methylpiperidino)-ethylaminol prepared according to the following method: a mixture 1-naphthylazo-quinoline. of 72 g (0.5 mole) of 1-naphthylamine, 80 g (0.51 mole) 2-(2-ethoxyethyl)-2-[4-(3-quinolylazo)-1- of 5-diethylamino-2-pentanone, 400 ml. of xylene and 1 naphthylamino-ethyl-amino-ethanol. g. of p-toluenesulfonic acid is boiled under reflux for 18 60 3-(4-(2-(hexahydro-2-methyl-1-pyridazinyl)-ethyl hours and the water which is formed is removed through amino]-1-naphthylazo-quinoline. a water separator. The reaction mixture is concentrated The other intermediate 1-naphthylamines employed in vacuo on the steam bath and the residue is dissolved in herein can be prepared from the appropriate 1-naphthol 300 ml. of methanol and hydrogenated in a Parr hydro or 1-naphthylamine precursors according to the proce genation apparatus in the presence of 2 g of palladium on dures described under Examples 1 through 15. carbon catalyst at an initial hydrogen pressure of 54 p.s.i.g. Additional quantities of palladium and platinum oxide Example 36 catalyst are added during the reduction as required. The 5-aminouracil (2.54 g., 0.02 mole) is diazotized and hydrogenation is complete after 6 hours. The catalyst coupled into 6.49 g. (0.02 mole) of N,N-diethyl-N'-1- is collected by filtration and the solvent removed in naphthyl-11-cyclohexanebis (methylamine) according to vacuo. Distillation of the residue through a 7-inch the procedure given under Example 1 herein for the Vigreux column in vacuo gives the desired N1,N1-diethyl preparation of 5-4-(2-diethylaminoethylamino)-1-naph N-1-naphthyl-1,4-pentanediamine as a yellow oil, B.P. thylazol-uracil. Crystallization of the crude dye from 149-151° C./0.2 mm., n25 1.5730. 75 ethanol containing a few drops of ammonium hydroxide 3,139,421 45 46 gives the desired 5-4-1-(diethylaminomethyl)-cyclo 1,1-cyclohexanebis(methylamine) is obtained as a viscous hexylmethylamino]-1-naphthylazouracil, of formula yellow oil, B.P. 161-162° C./0.07 mm. (CIs)..NCJ The other intermediate 1-naphthylamines employed N herein can be prepared from the appropriate 1-naphthol c11, 5 or 1-naphthylamine precursors according to the proce dures described under Examples 1 through 15. Example 37 2-methoxy - 5 - aminopyridine (3.72 g., 0.03 mole) is diazotized and coupled into 10.35 g. (0.03 mole) of deca 10 hydro - 1 - 2 - (1 - naphthylamino) - ethyl) - quinoline, monohydrochloride, according to the procedure outlined under Example 1 herein for the preparation of 5-4-(2-di ethylaminoethylamino)-1-naphthylazol - uracil. Crystal HO- N? OH O 5 lization of the crude dye from 2-propanol gives the de as red crystals, M.P. 219 C. (dec.). sired decahydro - 1 - {2 - 4 - (6 - methoxy - 3 - pyridyl Utilizing the preparative methods described under Ex azo)-1-naphthylamino-ethyl)-quinoline, of formula amples 1 through 15 herein, the following related com pounds can be prepared, starting from the appropriate amino or hydroxypyrimidine compound and substituted 20 1-naphthylamine precursors: 2,4,6-triamino-5-[4-(2-diethylaminoethylamino)- 1-napththylazo)-pyrimidine. 4-amino-5-4-(3-diethylamino-2,2-dimethylpropyl amino)-1-naphthylazo)-2-pyrimidinol. 6-amino-5-I4-(2-diethylaminoethylamino)-1- naphthylazol-uracil. 2-amino-5-4-(8-diethylaminooctylamino)-1- O CH3 naphthylazol-4,6-pyrimidinediol. N 2,6-diamino-5-[4-(2-diethylaminoethylamino)-1- 30 as yellow-orange crystals, M.P. 193.5-196° C. (dec.). naphthylazol-4-pyrimidinethiol. Utilizing the preparative methods described under Ex 4,6-diamino-5-[4-(2-methyl-3-piperidinopropylamino)- amples 1 through 15 herein, the following related con 1-naphthylazo)-2-pyrimidinol. pounds can be prepared, starting from the appropriate 4,6-diamino-5-[4-(2-diethylaminoethylamino)-1- substituted 1-naphthylamine and aminopyridine precur naphthylazo-2-(methylthio)-pyrimidine. SOIS: 5-4-(2-diethylaminoethylamino)-1-naphthylazo 1 - methyl - 4 - {methyl{2 - 4 - (3 - pyridylazo)-1-naph cytidine. thylaminol-ethyl-amino-piperidine. 4,6-diamino-5-4-(2-diethylaminoethylamino)-1- 5 - 4 - 2 - (isopropylmethylamino) - ethylamino - 6 naphthylazo)-2-pyrimidinethiol. methyl-1-naphthylazol-2-nitropyridine. 4-(2-amino-5-4-(2-diethylaminoethylamino)-1-naph 40 hexahydro - 1 - methyl - 2 - {2-4-(3-pyridylazo) - 1 thylazol-4-pyrimidinylamino-o-piperidino-o-cresol. naphthylamino-ethyl-pyridazine. 5-4-(2-diethylaminoethylamino)-1-naphthylazo octahydro - 2 - {2 - 4 - (3 - pyridylazo) - 1 - naphthyl 6-imino-3-phenylhydrouracil. amino-ethylcyclopentaclpyrrole. 2,4-dianilino-5-4-(3-piperidinopropylamino)-1- 2,2'- {2 - 4 - (3 - pyridylazo)-1-naphthylaminolethyl naphthylazol-pyrimidine. 45 imino-diethanol. N,N- diethyl- N' -1 - naphthyl - 1, 1 - cyclohexane 3-5 - bromo - 4 - (2 - diethylaminoethylamino) - 1 bis(methylamine), employed as a starting material in the naphthylazo-pyridine. above preparation, is synthesized as follows: tetrahydro 1 - methyl- 1 - {2 - 4 - (3 - pyridylazo) - 1 - naphthyl benzaldehyde (226 g., 2.05 moles), diethylamine hydro 50 amino-ethyl - 2,2'-bipiperidine. chloride (185 g., 1.69 moles), paraformaldehyde (78 g., 4 - {4 - (6 - ethoxy - 3 - pyridylazo) - 1 - naphthyl 2.6 moles) and 125 ml. of ethanol are boiled under re aminol-methyl-1-methylpiperidine. flux for 2 hours. An additional 78 g. of paraformalde 5 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazol hyde are added and reflux is continued for 6 hours. The 2-pyridinol. reaction mixture is poured into 2 1. of water and ex 3 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazo tracted with ether. The combined ether extracts are dis 2,6-dihydroxyisonicotinic acid. carded and the water layer is made alkaline by the addi 3 - 4 - (3 - piperidinopropylamino) - 1 - naphthylazo tion of sodium hydroxide. The oily layer which sepa 2,4,6-pyridinetriol. rates is extracted with ether and the combined ether ex 3- 4 - (2 - diethylaminoethylamino) - 1 - naphthlyazol tracts are dried over anhydrous potassium carbonate. The 60 2-oxonipecotic acid, ethyl ester. ether is removed on the steam bath and the residue is dis Decahydro - 1 - 2 - (1 - naphthylamino) - ethyl-quin tilled in vacuo to give the intermediate diethylamino oline, hydrochloride, employed as a starting material in the methyltetrahydrobenzaldehyde, of formula above preparation, is prepared from N-(2-bromoethyl)- CHO CHIN (CH) 1-naphthylamine, hydrobromide, and decahydroquinoline - according to the following procedure: N-(2-bromoethyl)- 1-naphthylamine, hydrobromide (173 g., 0.5 mole) is suspended in 500 ml. of concentrated ammonium hy droxide and the free base is extracted with several portions M of xylene. The Xylene extracts are dried over anhydrous as a yellow oil, B.P. 59-60° C./10.1 mm. np 1.4780. 70 sodium sulfate, the drying agent is removed by filtration, This intermediate is then condensed with 1-naphthylamine and the xylene solution is diluted to 750 ml. Decahydro and hydrogenated according to the procedure outlined un quinoline (137.2 g., 1.0 mole) and 1.5 1. of xylene are der Example 4 herein for the preparation of N,N-diethyl added, and the mixture boiled under reflux for 12 hours. 2.2 - dimethyl-N'-1-naphthyl-1,3-propanediamine. The The reaction mixture is cooled, 1 1. of 50% aqueous desired intermediate, N,N - diethyl- N' - 1 - naphthyl 75 sodium hydroxide is added, and the layers are separated. 3,189,421 47 48 The xylene layer is washed successively with 10% sodium 4- 4 - (2 - diethylaminoethylamino) - 1 - naphthylazol hydroxide solution and water and is dried over anhydrous 1,3-benzoxathiol - 5 - ol, 3,3,. - dioxide. sodium sulfate. The xylene is removed on the steam bath 1-2,2-dimethyl - 3 - (1-naphthylamino)-propyl-piper and the residue is distilled in vacuo to remove the excess dine, M.P. 76-77 C., employed as a starting material in decahydroquinoline. The residue is dissolved in 200 ml. 5 the above procedure, is prepared from 3-piperidinopiv of 2-propanol and the solution is treated with decolorizing aldehyde and 1-naphthylamine according to the procedure charcoal followed by an excess of a 2-propanol-hydrogen outlined under Example 4 herein for the preparation of chloride mixture. The precipitate which forms is col N,N-diethyl - 2,2 - dimethyl-N'-1-naphthyl-1,3-propane lected by filtration, washed with 2-propanol, and crystal diamine. The other substituted 1-naphthylamine inter lized from a methanol-2-propanol mixture. The colorless O crystals thus obtained, M.P. 252-254 C., are the de mediate employed herein can be prepared from the ap sired intermediate, decahydro - 1 - 2 - (1 - naphthyl propriate 1-naphthylamine or 1-naphthol compound ac amino)-ethyl]-quinoline, monohydrochloride. cording to the procedure described under Examples 1 The other intermediate 1-naphthylamines employed through 15. herein can be prepared from the appropriate 1-naphthol Example 39 or 1-naphthylamine precursors according to the proce 5 4-aminoantipyrine (6.1 g., 0.03 mole) is diazotized and dures described under Examples 1 through 15. coupled into 12.3 g (0.03 mole) of 4-2-(1-naphthyl amino)-ethyl)-1-piperazineethanol, trihydrochloride, ac Example 38 cording to the procedure outlined under Example 3 here 1-thianthrenamine (0.89 g., 0.0038 mole) is diazotized in for the preparation of 5-4-(2-(2-diisopropylamino and coupled into 1.03 g (0.0038 mole) of 1-2,2-dimethyl 20 ethyl) - methylaminol - ethylamino - naphthylazo-inda 3-(1-naphthylamino)-propyl-piperidine according to the zole, Crystallization of the crude dye from 2-propanol procedure outlined under Example 3 herein for the prep gives the desired 4-(4-2-[4-(2-hydroxyethyl) - 1 - pipera aration of 5-4-(2-(2 - diisopropylaminoethyl)-methyl zinyl - ethylamino - 1 - naphthylazo - 2,3-dimethyl-1- amino - ethylamino - 1 - naphthylazo) - indazole. Crys phenyl-3-pyrazolin-5-one, of formula tallation of the crude dye from a dimethylacetamide-water 25 mixture gives the desired 1-(2,2-dimethyl - 3 - 4 - (1- thianthrenylazo) - 1 - naphthylamino-propyl-piperidine, of formula CFI 30 NHCH- CFIN/ 2 CH

35 -N

40 COO as fibrous yellow-orange crystals, M.P. 180.5-1815 C. as deep maroon crystals, M.P. 80° C. (dec.). Utilizing the preparative methods described under Ex Utilizing the preparative methods described under Ex amples 1 through 15 herein, the following related com amples 1 through 15 herein, the following related com 45 pounds can be prepared, starting from the appropriate pounds can be prepared, starting from the appropriate sub substituted 1-naphthol or 1-naphthylamine and pyrazole stituted 1-naphthylamine and amino-4,5-benzodioxole, compounds: amino - 1,3-benzodioxane, amino - 1,4-benzodioxane, 1-(2,5-dichlorophenyl)-3-methyl-4-4-(1-methyl-4-piper amino -1,3-benzoxathiole, aminophenoxathiin, or amino idinylamino)-1-naphthylazol-2-pyrazolin-5-one. thianthrene: 50 m-(4-4-(2-diethylaminoethylamino)-1-naphthylazol-5- N,N- diethyl- N'-[4-(1 - thianthrenylazo)-1-naphthyl hydroxy-3-methyl-1-pyrazolyl)-N-2-hydroxyethyl ethylenediamine. N-methylbenzenesulfonamide. 1 - 6 - chloro - 4 - 2 - (isopropylmethylamino)-ethyl 5-hydroxy-4-(4-(2-2-(2-methoxyethoxy)-ethyl-methyl aminol-1-naphthylazo-3-phenoxathiincarboxylic acid. amino-ethylamino-1-naphthylazo-3-pyrazole N,N- diethyl - 2,2-dimethyl- N'-[4-(2-phenoxathi carboxylic acid, ethyl ester. inylazo) - 1 - naphthyll - 1,3 - propanediamine. 2-4-(4-(2-diethylaminoethylamino)-1-naphthylazo-3- N',N'- diethyl - N - 4 - (2 - thianthrenylazo) - 1 methyl-5-oxo-2-pyrazolin-1-yl)-6-methyl-7- naphthyl-1,2-propanediamine. benzothiazolesulfonic acid. 1,14 triethyl - 7 - 4 - (2 - phenoxathiinylazo) - 1 60 1-3-(7-bromo-4-1-(p-chlorophenyl)-3-methyl-4-pyra naphthyl-diethylenetriamine, 10,10-dioxide. zolylazol-1-naphthylamino-2-methylpropyl N,N- diethyl- N'-(4 - (3,4 - methylenedioxyphenyl piperidine. azo) - 1 - naphthyll - ethylenediamine. 2,5-dichloro-4-4-4-(2-diethylaminoethylamino)-1- N4-(1,4-benzodioxane - 6-ylazo) - naphthyl-N, naphthylazol-3-methyl-5-oxo-2-pyrazolin-1- N-diethylethylenediamine. yl)-benzenesulfonic acid. 8 (4- (2 - diethylaminoethylamino) - 1 - naphthylazo 4-4-(2,2-dimethyl-3-(4-methyl-1-piperazinyl)-propyl 2-phenoxathiinol, 10,10-dioxide. amino-1-naphthylazo)-5-hydroxy-1-(p-nitrophenyl)- 1 - diethylamino - 3 - 4 - (4.5 - methylenedioxy - o 3-pyrazolecarboxylic acid. tolyazo) - 1 - naphthylamino)-2-propanol. 6-(4-(4-(2-(ethyl(3-methoxypropyl)-aminol-ethylami N,N-diisopropyl- N' - 4 - (4 - phenoxathiinylazo) - 1 70 no-1-naphthylazo)-5-hydroxy-3-methyl-1-pyrazolyl)- naphthyl-ethylenediamine. 1,3-naphthalenedisulfonic acid. N' - 4 - (1,3-benzodioxane-6-ylazo) - 1 - naphthyll 3-amino-4-[4-(2-diethylaminoethylamino)-1-naphthyl N,-diethylethylenediamine. azol-5-pyrazolol. 4 - 2 - 4 - (7-methoxy - 1,4-benzodioxan - 6-ylazo)- 3-(4-4-(2-diethylaminoethylamino)-1-naphthylazol-5- 1 - naphthylamino - ethyl - 1 - piperazineethanol. 75 hydroxy-3-methyl-1-pyrazolyl)-dibenzenesulfonamide. 3,139,421 49 50 3-amino-4-4-(2-diethylaminoethylamino)-1-naphthyl The other intermediate 1-naphthylamines employed azol-1-phenyl-2-pyrazolin-5-one. herein can be prepared from the appropriate 1-naphthol p-4-4-2-(isopropylmethylamino)-ethylaminol-1-naph or 1-naphthylamine precursors according to the proced thylazo-5-hydroxy-3-methyl-1-pyrazolyl)-benzene ures described under Examples 1 through 15. sulfonic acid. 4-4-(2-diethylaminoethylamino)-1-naphthylazol-5- Example 41 hydroxy-3-methyl-1-pyrazolecarboxamidine. 3-aminopyridine (5.7 g., 0.06 mole) is diazotized and coupled into 14.4 g (0.06 mole) of 1-methyl-4-(1-naph 1-(2-imidazolin-2-yl)-4-(4-2-(isopropylmethylamino)- thylamino)-piperidine according to the procedure speci ethylamino-1-naphthylazo-3-methyl-5-pyrazolol. fied under Example 3 herein for the preparation of 5-(4- 4-2-(1-naphthylamino)-ethyl) - 1 - piperazineethanol, 10 {2-(2-diisopropylaminoethyl)-methylaminol - ethyl trihydrochloride, M.P. 207-211. C., employed as a start amino-1-naphthylazo-indazole. Crystallization of the ing material in the above preparation is prepared from N-(2-bromoethyl)-1-naphthylamine, hydrobromide, and crude dye from 2-propanol gives the desired 1-methyl-4- 1-piperazineethanol according to the procedure described 4- (3-pyridylazo)-1-naphthylaminol-piperidine, of under Example 37 herein for the preparation of decahy 15 formula dro-1-(2-(1 - naphthylamino) - ethyl) - quinoline, hydro NH- 3-c H chloride. The other intermediate 1-naphthylamines em ployed herein can be prepared from the appropriate 1 naphthol or 1-naphthylamine precursors according to the procedures described under Examples 1 through 15. 20 Example 40 5-amino-2,1,3-benzothiadiazole (1.5 g., 0.01 mole) is diazotized and coupled into 2.4 g. (0.01 mole) of 1-(2- e diethylaminoethylamino)-naphthalene according to the 25 procedure outlined under Example 3 herein for the prepa as orange-red crystals, M.P. 169.5-171 C. ration of 5-4-2 - (2 - diisopropylaminoethyl)-methyl Utilizing the preparative methods outlined under Ex amino-ethylamino - 1 - naphthylazo-indazole. Crystal amples 1 through 15 herein, the following related com lization of the crude dye from a methanol-2-propanol pounds can be prepared, starting from the appropriate mixture gives red crystals of the desired 5-4-(2-diethyl 30 aminopyridine and substituted 1-naphthylamine precur aminoethylamino) - 1 - naphthylazo)-2,1,3-benzothiadia SOS: zole, of formula 2 - (2 - ethoxyethyl)-2-[4-(3-pyridylazo)-1-naphthyl aminol-ethyl-amino-ethanol. NH(CII).N.C.H.), 35 3 - {4 - (2-hexahydro-1-indolinyl)-ethylamino]-1-naph thylazo-picolinic acid. 3 - {4 - {2-bis(2-dimethylaminoethyl)-amino-ethyl amino)-1-naphthylazo-4-(phenylthio)-pyridine. N 5 - 4 - (1-ethyl-4-piperidylamino)-1-naphthylazol-2-py 7 40 ridinol. N 3 - {4- {2-[2-(2-ethoxyethoxy)ethyl)-ethylamino-ethyl ls / amino)-1-naphthylazo-pyridine. N 2 - 5 -bromo - 4-(2-(3-methoxy-1-pyrrolidinyl)-ethyl amino-1-naphthylazo-pyridine. Utilizing the preparative methods described under Ex 45 5 - 4 - (2-diethylaminoethylamino)-7-methoxy-1-naph amples 1 through 15 herein, the following related com thylazo)-2-methoxypyridine. pounds can be prepared, starting from the appropriate or - Methyl - 1 - {2-[4-(3-pyridylazo)-1-naphthylaminol substituted 1-naphthylamine and benzothiadiazole, benz ethyl-3-piperidinemethanol. isothiazole, or thieno 3,2-b-pyridine compound: 2 - {2 - {methyl{2-[4-(3-pyridylazo)-1-naphthylaminol 50 ethyl)-amino-ethoxy-ethanol. 5-(4-2-(hexylmethylamino)-ethylamino-1-naphthyl 2 - chloro-5-4-(2-(2-(2-diethylaminoethoxy)-ethyl]- azo-1,2,3-benzothiadiazole. ethylamino-ethylamino-1-naphthylazo)-pyridine. 4-4-(2-diethylaminoethylamino)-1-naphthylazo)-2,1,3- 3 - 4 - {2-(bis(2-methylallyl)-aminol-ethylamino)-1- benzothiadiazole. naphthylazo-pyridine. 5-(4-2-(ethylisopropylamino)-ethylamino]-1-naphthyl 55 1,1' - {3 - 4-(3-pyridylazo)-1-naphthylaminol-propyl azo)-1,2-benzisothiazole. iminobis(trimethylene)-dipiperidine. 6-4-(2-dimethylamino-1-methylethylamino)-1-naphthyl 3 - {4 - 2-(isopropylmethylamino)-ethylamino]-6-methyl azol-1,2-benzisothiazolin-3-one, 1,1-dioxide. 1-naphthylazo-pyridine. 6-(4-(2-(2-ethoxyethyl)ethylamino-ethylamino)-1- 1 - methyl-4-(1-naphthylamino)-piperidine, B.P. 144 naphthylazo-1,2,3-benzothiadiazole. 60 146 C./0.2 mm., employed as a starting material in the 3-(4-2-(1-pyrrolidinyl)-ethylamino]-1-naphthylazo above preparation, is prepared from 1-methyl-4-piperi thieno3,2-b-pyridine. done and 1-naphthylamine according to the procedure de 4-amino-7-4-(3-diethylamino-2,2-dimethylpropylami scribed under Example 34 herein for the preparation of no)-1-naphthylazol-1,2,3-benzothiadiazole. N,N1 - diethyl- N'-1-naphthyl-1,4-pentanediamine. The 5-4-(2-diethylaminoethylamino)-6-methoxy-1-naphthyl 65 other intermediate 1-naphthylamines employed herein can azo-3-phenyl-1,2-benzisothiazole. be prepared from the appropriate 1-naphthol or 1-naph 5-amino-4-4-(2-diethylaminoethylamino)-1-naphthyl thylamine precursors according to the procedures de azo]-1,2,3-benzothiadiazole. 1-4-(2,1,3-benzothiadiazol-5-ylazo)-1-naphthylamino scribed under Examples 1 through 15. 3-diethylamino-2-propanol. 70 Example 42 4-4-2-(isopropylmethylamino)-ethylamino)-1-naph 3-aminoquinoline (2.9 g., 0.02 mole) is diazotized and thylazo)-2,1,3-benzothiadiazole. coupled into 7.7 g (0.02 mole) of 1,1,7,7-tetraethyl-4-2- 6-4-2-4-2-(1-pyrrollidinyl)-ethyl)-piperidino-ethyl (1-naphthylamino)-ethyl-diethylenetriamine according to amino-1-naphthylazo-1,2-benzisothiazolin-3-one, the procedure outlined under Example 6 herein for the 1,1-dioxide. 75 preparation of 1-diethylamino-3-(4- (3-pyridylazo)-1- 3,139,421 naphthylamino)-2-propanol,51 trihydrochloride.s Crystalli 52 zation of the crude dye from a methanol-2-propanol mix yl)- ethylamino]-1-naphthylazo-1,2-benzisothiazole, of ture containing a few drops of ethanolic hydrogen chlo formula, ride gives the desired 3-4-(2-bis(2-diethylamino-ethyl)- amino-ethylamino-1-naphthylazoquinoline, pentahy -- drochloride, of formula, NH(CEI)N22 /SN N 0. N=N

Utilizing the preparative methods described under Ex 5 amples 1 through 15 herein, the following related com pounds can be prepared, starting from the appropriate substituted 1-naphthylamine and benzothiazole, benziso thiazole, benzoxazole, or naphthoxazole: 20 6 - 4 - (2-diethylaminoethylamino)-1-naphthylazol-ben zothiazole. as a reddish-purple hydrated solid, M.P. 155-163 C. 3 - methyl - 6-4-(1-methyl-4-piperidylamino)-1-naph (dec.). thylazol-2-benzoxazolinone. Utilizing the preparative methods described under Ex 2 - {{2 - 4-(2-chloro-6-benzothiazolylazo)-1-naphthyl amples 1 through 15 herein, the following related com 25 aminol-ethyl)-pentylamino-ethanol. pounds can be prepared, starting from the appropriate 4 - {4 - 2 - (allylethylamino)-ethylamino-1-naphthyl aminoquinoline and substituted 1-naphthylamine precur azo-benzothiazole. SOS 5 - 6 - chloro-4-(2-diethylaminoethylamino)-1-naphthyl 3 - {4 - 2 - (1 - azaspiro4.4) non-1-yl)-ethylamino)-1- azol-2-benzoxazolinone. naphthylazo-quinoline. 30 4 - 4 - (7-diethylaminoheptylamino)-1-naphthylazo)-6- 7 -azo-quinoline. {4 - 2-(2-piperidinoethoxy)-ethylamino]-1-naphthyl methoxy-2-benzothiazolecarboxylic acid. 8 - 4 - (3-diethylamino-2-methoxypropylamino)-1-naph 4 -naphthylazo)-2-methylbenzoxazole. 4 - 2 - (cyclopentylmethylamino)-ethylamino]-1- thylazo).5,6-dimethoxyquinoline. 1 - 3 - 4 - (2-acetamido-5-benzothiazolylazo)-1-naph 5 - 4 - (2-methyl-2-piperidinopropylamino)-1-naphthyl thylamino-2,2-dimethylpropyl-4-methylpiperazine. azol-quinoline. 9 - 4 - (2-diethylaminoethylamino)-1-naphthylazo)-8- 3 - 7 - chloro-4-(2-diethylaminoethylamino)-1-naphthyl hydroxynaphth 1,2)-oxazoline-2-thione. azo-quinoline. 4 - amino - 7-4-(2-diethylaminoethylamino)-1-naphthyl 1 - {2 - 4-(5-phenylazo-8-quinolylazo)-1-naphthyl azobenzothiazole. amino-ethyl-3-piperidinemethanol. 40 3 - 4 - (m- diethylaminoanilino)-1-naphthylazol-quino 2 -naphthylazo)-benzothiazole. amino - 6-4-2-(4-methylpiperidino)-ethylamino-1- line. 3 - 4 - (2-diethylaminoethylamino)-6-methoxy-1-naph 6 - {4 - 2 - hydroxy-3-(isopropylmethylamino)-propyl thylazo-quinoline. amino]-1-naphthylazo)-2-benzoxazolinone. 45 The starting material, 1-2-(1-naphthylamino)-ethyl 3 amino)-1-naphthylazo-quinoline.- 4 - {2 -[2-(2-diethylaminoethoxy)-ethoxy-ethyl pyrrolidine, B.P. 142-143 C./0.1 mm., n25 1.6183, is 1 - {ethyl{2 - 4 - (3 - quinolylazo) - 1-naphthylamino prepared from 1-naphthylamine and N-(2-chloroethyl)- ethyl-amino)-2-propanol. pyrrolidine, hydrochloride, according to the procedure 8 - chloro - 6-4-2-ethyl (2-hydroxy-3-methoxypropyl)- outlined under Example 1 herein for the preparation of amino - ethylamino - 1 - naphthylazo-4-methylcar 50 1-(2-diethylaminoethylamino)-naphthalene. The other bostyril. intermediate 1-naphthylamines employed herein can be 5 - (3 - quinolylazo)-8-(2-diethylaminoethylamino)-1- prepared from the appropriate 1-naphthol or 1-naphthyl naphthol. anine precursors according to the procedures described 1, 1,7,7 - tetraethyl-4-2-(1-naphthylamino)-ethyl)-di under Examples 1 through 15. ethylenetriamine, B.P. 176-177 C./0.1 mm., n25 1.5563, 55 Example 44 employed as an intermediate in the above procedure, is prepared from N-(2-bromoethyl)-1-naphthylamine, hy To a solution of 7.3 g (0.05 mole) of 2-aminopyridine, drobromide and 1,1,7,7- tetraethyldiethylenetriamine ac 1-oxide, hydrochloride in 300 ml. of water containing 13 cording to the method described under Example 3 herein ml. (0.15 mole) of concentrated hydrochloric acid is for the preparation of 1,1-diisopropyl-4-methyl-7-(1- 60 added a solution of 3.5 g. (0.05 mole) of sodium nitrile naphthyl)-diethylenetriamine. The other intermediate 1 in 50 ml. of water while maintaining the temperature at naphthylamines employed herein can be prepared from -3 to 2 C. Stirring is continued at this temperature the appropriate 1-naphthol or 1-naphthylamine precursors for one-half hour and the yellow diazonium salt solution according to the procedures described under Examples 1 is added portionwise to a solution of 12.1 g (0.05 mole) through 15. 65 of N,N- diethyl - 2 - methyl-N'-1-naphthyl-1,3-propane Example 43 diamine in 200 ml. of 95% ethanol, keeping the tempera ture between -5 and 5 C. After one-half hour, the 5-amino-1,2-benzisothiazole (1.5 g., 0.01 mole) is dia reaction mixture is diluted with water to a volume of zotized and coupled into 2.4 g (0.01 mole) of 12-1-naph 3 l., made strongly alkaline with concentrated sodium thylamino)-ethyl)-pyrrolidine according to the procedure 70 hydroxide, and the oily precipitate is extracted with sev outlined under Example 3 herein for the preparation of eral portions of chloroform. The combined chloroform 5 - {4 - {2-((2-diisopropylaminoethyl)-methylaminol extracts are washed with water, dried over anhydrous ethylamino-1-naphthylazo-indazole. Crystallization of potassium carbonate, and concentrated on the steam bath. the crude dye from a methanol-2-propanol mixture gives Crystallization of the crude dye thus obtained from a orange-red crystals of the desired 5-4-2-(1-pyrrolidin 75 methanol-acetonitrile mixture gives the desired 2-[4-(3- 3,139,421 53 54 dimethylamino - 2 - methylpropylamino)-1-naphthylazo removed and the residue distilled in vacuo through an pyridine, 1-oxide, of formula, 8-inch Vigreux column. The desired N,N-diethyl-2-meth yl-N'-1-naphthyl-1,3-propanediamine is obtained as a yellow oil, B.P. 117-118° C./0.15 mm., which solidifies CH in the receiver. NHCH, HCHNC H3)2 Alternatively, the alkylation may be carried out in the presence of sodium amide according to the following procedure: in a 2 1.3-necked flask fitted with a mechani cal stirrer, condenser, thermometer and addition funnel 0. is placed 40 g. (1 mole) of sodium amide and 500 ml. of dry toluene. A solution of 72 g. (0.5 mole) of 1-naph NeN thylamine in 300 ml. of toluene is then dripped into the mixture with mechanical stirring. The addition is not exothermic. The reaction mixture is then boiled under 02) 5 reflux for 1 hour, whereupon a thick greenish-black gum precipitates along the sides of the flask. A solution of as green crystals with a red luster, M.P. 185-186 C. 0.58 mole of 3-dimethylamino-2-methylpropylchloride in (dec.). 200 ml. of toluene, prepared as described above, is then Utilizing procedures similar to those described in Exam added at room temperature to the sodium amide-naphthyl ples 1 through 15 herein, the following related compounds 20 amine mixture; the addition is mildly exothermic. When can be prepared, starting from the appropriately substi the addition of the halide is complete, the reaction mixture tuted 1-naphthylamine and aminopyridine-1-oxide or is stirred and boiled under reflux for 3 hours. Upon aminoquinoline-1-oxide compounds: cooling, 300 ml. of water is cautiously added and the 4 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazo product is worked up as described above to give the quinoline, 1-oxide. 25 desired N,N-diethyl-2-methyl-N'-1-naphthyl-1,3-propane 3-4-2-(isopropylmethylamino)-ethylamino]-1-naphthyl diamine as a yellow oil, B.P. 124-125 C./0.3 mm. azo-pyridine, 1-oxide. The other intermediate 1-(dialkylaminoalkylamino)- 3-(4-(2-((2-ethoxyethyl) - ethylaminol - ethylamino)-1- naphthalenes employed herein can be prepared from the naphthylazo-quinoline, 1-oxide. appropriate naphthalene compound according to the 1 - 3 - 7 - methoxy - 4 - (2 - methyl - 4 - pyridylazo)- 30 procedures described under Examples 1 through 15 herein. 1-naphthyl)-propyl-piperidine, 1-oxide. 3 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazo Example 45 quinoline, 1-oxide. 3-aminoacridine (1.94 g., 0.01 mole) is diazotized and 2 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazo coupled into 2.82 g (0.01 mole) of N-cyclohexyl-N- pyridine, 1-oxide. 35 methyl-N'-1-naphthylethylenediamine according to the 4 - amino - 6 - 4 - (2 - diethylaminoethylamino)-1- procedure outlined under Example 3 herein for the prep naphthylazo-quinoline, 1-oxide. aration of 5-(4-(2-(2-diisopropylaminoethyl)-methyl 4 - 6 - chloro - 4 - (3 - diethylamino - 2,2 - dimethyl aminol-ethylamino-1-naphthylazo-indazole. Crystalli propylamino)-1-naphthylazol-pyridine, 1-oxide. zation of the crude dye from an acetonitrile-water mixture 3 - {4 - {2 - 4 - (2 - piperidinoethyl) - piperidino - ethyl 40 gives the desired 3-4-2-(2-cyclohexylmethylamino)- amino-1-naphthylazo-quinoline, 1-oxide. ethylamino]-1-naphthylazo-acridine, of formula, 2 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazol pyridine, 1-oxide. 4 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazo CH pyridine, 1-oxide. 45 3 -84 - 2 - isopropylmethylamino) - ethylamino)-1- naphthylazo-quinoline, 1-oxide. Nichol-C) The starting material, N,N-diethyl-2-methyl-N'-1-naph thyl-1,3-propanediamine, can be prepared as follows: in 50 a 2-l. 3-necked flask fitted with a mechanical stirrer, con denser and dropping funnel is placed a suspension of 36 g. (0.75 mole) of 50% sodium hydride in oil dispersion in 200 ml. of xylene. A solution of 72 g (0.5 mole) of 1-naphthylamine in 300 ml. of xylene is then added, and 55 the mixture is stirred and boiled under reflux for 2 hours, as orange-red crystals. during which time the thick green sodium salt precipitates. Utilizing the preparative methods described under Ex The reaction mixture is allowed to cool to room tempera amples 1 through 15 herein, the following related com ture. Meanwhile, 100 g. (0.58 mole) of 3-dimethylamino pounds can be prepared, starting from the appropriate 2-methylpropylchloride, hydrochloride is suspended in 200 60 Substituted 1-naphthylamine and aminoacridine com ml. of concentrated ammonium hydroxide and the base pound: which separates is extracted with three 100 ml. portions 3,6-diamino-4-(4-(2-diethylaminoethylamino)- of xylene. The combined extracts are dried over an 1-naphthylazol-acridine. hydrous sodium sulfate, the drying agent is collected by 2-4-2-[4-(2-diethylaminoethyl)-1-piperazinyl]- filtration, and the xylene filtrate is cautiously added with 65 ethylamino-1-naphthylazo-1,4-dimethoxy stirring to the sodium hydride-naphthylamine mixture. 9-acridanone. The addition is not exothermic. After the addition is com 4-[4-(2-diethylaminoethylamino)-1-naphthylazol-3,6- plete, the mixture is stirred and boiled under reflux for 20 bis(dimethylamino)-acridine. hours. The deep brown reaction mixture is cooled to room 4-[4-(2,3-dipiperidinopropylamino)-1-naphthylazo temperature and 200 ml. of water is cautiously added with 70 acridine. stirring. The aqueous layer which separates is discarded 1-(2-diethylaminoethylamino)-4-(4-(2-dimethylamino and the organic layer is washed with two 200 ml. portions ethylamino)-1-naphthylazol-acridine. of water to remove any undissolved salts. The xylene 2,2'-(2-4-9-(2-diethylaminoethylamino)-7-methoxy extracts are dried over anhydrous potassium carbonate, 3-acridinylazol-1-naphthylamino-ethylimino the drying agent is collected by filtration, the solvent is .75 diethanol, 3,139,421. 55 56 9-4-2-[4-(2-piperidinoethyl)-piperidino)-ethylamino pounds can be prepared, starting from the appropriate 1-naphthylazo-acridine. substituted naphthylamine precursor and aminothiadiazole 3-chloro-9-(3-diethylaminopropylamino)-6-[4-(2-di or aminotriazole: ethylaminoethylamino)-1-naphthylazo)-acridine, 2-4-(2-diethylaminoethylamino)-1-naphthylazol-5- 1-oxide. methyl-1,3,4-thiadiazole. 6-7-methoxy-4-(2-(3-methoxy-1-pyrrolidinyl)-ethyl 3-(4-2-(1-pyrrolidinyl)-ethylaminol-1-naphthylazo amino]-1-naphthylazo)-9-oxo2-acridansulfonic acid. s-triazole. 6-chloro-2-(4-2-[(2-diethylaminoethyl)-ethylaminolethylamino-1-naphthylazo-acridine. 2-4-(2-dimethylamino-1-methylethylamino)-1-naph 1-diethylamino-3-(6-4-(2-diethylaminoethylamino)- thylazol-5-nitro-1,3,4-thiadiazole. 1-naphthylazol-2,3-dimethoxy-9-acridinylamino 10 5-4-(2-diethylaminoethylamino)-1-naphthylazol-s- 2-propanol. triazole-3-carboxylic acid. 3,6-diamino-4-4-(5-dimethylaminopentylamino)-1- 2-nitro-5-4-(3-piperidinopropylamino)-1-naphthylazol naphthylazol-2,7-dimethylacridine. 3-4-(2-diethylaminoethylamino)-1-naphthylazol-5-1,3,4-thiadiazole. N-cyclohexyl- N - methyl- N' - 1-naphthylethylenedi 5 phenyl-s-triazole. amine, B.P. 167-168 C./0.2 mm., n25 1.5984, employed 2-[4-(1-methyl-4-piperidylamino)-1-naphthylazo - 1,3,4- as a starting material in the above procedure, is prepared thiadiazole. from N-(2-bromoethyl)-1-naphthylamine, hydrobromide, 2-4-(3-diethylamino-2,2-dimethylpropylamino)-1- and N-methylcyclohexylamine according to the procedure naphthylazol-5-phenyl-1,3,4-thiadiazole. described under Example 3 herein for the preparation 20 3-4-(2-diethylaminoethylamino)-1-naphthylazol-1,2,5- of 1,1-diisopropyl-4-methyl - 7 - (1-naphthyl)-diethylene thiadiazole. triamine. The other intermediate 1-naphthylamines em 2-4-(2-diethylaminoethylamino)-1-naphthylazo ployed herein can be prepared from the appropriate s-triazole. 1-naphthol or 1-naphthylamine precursors according to 2-4-[2-(1-methyl-2-piperidyl)-ethylaminol-1-naph 25 thylazol-5-styryl-1,3,4-thiadiazole. the procedures described under Examples 1 through 15. 2-4-(4-diethylaminocyclohexylamino)-1-naphthylazo Example 46 5-nitro-1,3,4-thiadiazole. Sodium nitrate (3.0 g., 0.043 mole) is added portion The other intermediate 1-naphthylamines employed wise to 20 ml. of concentrated sulfuric acid, with stirring, 30 herein can be prepared from the appropriate 1-naphthol and the temperature of the reaction mixture is allowed or 1-naphthylamine precursors according to the pro to rise to 65° C. The resulting solution is cooled to cedures described under Examples 1 through 15. 5 C. and is treated dropwise, with stirring, with 40 ml. of a mixture of 6 ml. of propionic acid and 34 ml. of Example 47 acetic acid while allowing the temperature to rise to 35 A solution of 11.5 g. (0.1 mole) of 5-amino-3-methyl 15° C. The reaction is maintained at this temperature 1,2,4-thiadiazole in 250 ml. of 50% sulfuric acid is cooled during the remainder of the addition. The above nitro to -5° C. and diazotized by the portionwise addition syl sulfuric acid mixture is cooled to 0 to -5° C. and of 6.9 g. (0.1 mole) of sodium nitrite dissolved in 50 ml. treated with 6.0 g. (0.04.1 mole) of 2-amino-5-nitro of ice water. When diazotization is complete, the di 1,3,4-thiadiazole portionwise, with stirring, after which 40 40 azonium salt mixture is added to the solution of 33.1 g. ml. of a propionic-acetic acid mixture prepared as de (0.1 mole) of N,N-bis(2-ethoxyethyl)-N'-1-naphthyl scribed above are added while maintaining the tempera ethylenediamine in 1 1. of water containing 50 ml. of con ture of the reaction mixture between 0° C. and -5° C. centrated hydrochloric acid, maintaining the temperature The reaction mixture thus obtained is then stirred at at 0° C. during the addition. The deep purple mixture 0 C, to -5° C. for 2 hours and excess nitrite present 45 is stirred at 0-5 C. for 4 hours and is made alkaline is destroyed by the addition of urea. The clear diazonium with concentrated ammonium hydroxide. The super solution thus obtained is added, with stirring, at 0° C. natant is decanted from the red base, and the residue is to -5° C. to a solution of 9.8 g. (0.04.1 mole) of 1-(2- washed thoroughly with water and crystallized from an diethylaminoethylamino)-naphthalene in a mixture of 10 acetonitrile- water mixture to give the desired 5-(4-(2- ml. of propionic acid and 60 ml. of acetic acid. After 50 bis(2-ethoxyethyl)-amino-ethylamino-1-naphthylazo a short time, the reaction mixture is made neutral to 3-methyl-1,2,4-thiadiazole, of formula, Congo Red paper by adding sodium acetate portionwise and the coupling reaction is allowed to proceed for 1 hour. The reaction mixture is diluted with 2 1. of 1% NH(CH2)N(CH2CHO CH) sodium hydroxide and allowed to stir at room tempera 55 ture for 16 hours. The precipitated azo compound is collected by filtration and wash thoroughly with water. Crystallization of the crude dye from an acetonitrile-water mixture gives shimmering crystals of the desired 5-4-(2- diethylamino)-1-naphthylazol-2-nitro - 1,3,4 - thiazole, of formula, 60

NH(CEI2)N(CIIs) Utilizing the preparative methods outlined under Ex 65 amples 1 through 15 herein, the following related com pounds can be prepared, starting from the appropriate substituted 1-naphthylamine precursors and aminothiadi N-N azole, aminooxadiazole, aminoimidazole, or aminoisoxa CO zole: -- NO 70 Ns/-Nui 5-4-(2-diisopropylaminoethylamino)-1-naphthylazol3-methyl-1,2,4-thiadiazole. 5-4-(2-diethylaminoethylamino)-1-naphthylazo-3- methyl-1,2,4-oxadiazole. Utilizing the preparative methods outlined under Ex amples 1 through 15 herein, the following related com 4-4-2-(ethylmethylamino)-ethylamino]-1-naphthylazo5-methylimidazole. 3,139,421 57 58 5-(4-(2-diethylaminoethylamino)-7-methoxy-1- 1-(2-dibutylaminoethylamino)-4-(4-(2-diethylamino naphthylazo-3-phenyl-1,2,4-thiadiazole. ethylamino)-1-naphthylazol-10-thiaxanthenone. 2-ethyl-5-[4-(2-morpholinoethylamino)-1-naphthylazo 3-4-(2-diethylaminoethylamino)-1-naphthylazol-4- 4-imidazolecarboxylic acid, ethyl ester. hydroxycoumarin. 4-4-(3-diethylamino-2-methylpropylamino)-1- 3-(4-(3-dimethylamino-2-hydroxypropylamino)-1- naphthylazol-5-methyl-1,2,3-thiadiazole. naphthylazol-9-xanthenone. 4-4-(2-diethylaminoethylamino)-1-naphthylazo]-1,5- 8-4-(2-diethylaminoethylamino)-1-naphthylazol-7- dimethylimidazole. hydroxy-3-methoxyflavone. 2-ethyl{2-4-(1,2,3-thiadiazol-5-ylazo)-1- 1-4-2-(isopropylmethylamino)-ethylamino]-1- naphthylamino-ethyl-amino-ethanol. O naphthylazo)-4-methylxanthene. 4-4-(3-dimethylaminopropylamino)-1-naphthylazol-2- The other intermediate 1-naphthylamines employed phenyl-5-imidazolecarboxylic acid, ethyl ester. herein can be prepared from the appropriate 1-naphthol 1-methyl-4-2-4-(1,2,4-thiadiazol-3-ylazo)-1- or 1-naphthylamine precursors according to the proce naphthylamino-ethyl-piperazine. dures described under Examples 1 through 15. 5-7-chloro-4-(2-diethylaminoethylamino)-1- 5 naphthylazo-3-methoxy-1,2,4-thiadiazole. Example 49 5-I4-(2-diethylaminoethylamino)-1-naphthylazo-3,4- 7-aminocinnoline (1.45 g., 0.01 mole) is diazotized and dimethylisoxazole. coupled into 2.54 g (0.01 mole) of N-allyl-N-ethyl-N-1- N,N'-bis(2- ethoxyethyl) - N' - 1 - naphthylethylene naphthylethylenediamine according to the procedure out diamine, B.P. 157-158° C./0.07 mm., n25 1.5598, em 20 lined under Example 1 herein for the preparation of 5-4- ployed as a starting material in the above procedure, is (2-diethylaminoethylamino)-1-naphthylazol-uracil. Crys prepared from 1-(2-bromoethyl)-1-naphthylamine, hydro tallization of the crude dye from a methanol-isopropanol bromide and bis(2-ethoxyethyl)-amine according to the mixture gives red crystals of the desired 7-4-(2-allylethyl procedure described under Example 3 herein for the prep amino)-ethylamino-1-naphthylazo}-cinnoline, of for aration of 1,1-diisopropyl-4-methyl-7-(1-naphthyl)-di 25 mula, ethylenetriamine. The other intermediate 1-naphthyl amines employed herein can be prepared from the appro CHCH priate 1-naphthol or 1-naphthylamine precursors accord NH(CH2)N ing to the procedures described under Examples 1 through CHCH=CH, 15. 30 Example 48 1-amino-4-methyl-10-thiaxanthenone (4.8 g., 0.02 mole) is diazotized and coupled into 4.8 g. (0.02 mole) -- N of 1-(2-diethylaminoethylamino)-naphthalene according 35 N=N NN/ to the procedure outlined under Example 1 herein for the preparation of 5-4-(2-diethylaminoethylamino)-1-naph thylazol-uracil. Crystallization of the crude dye from Utilizing the preparative methods described under Ex acetonitrile gives red crystals of the desired 1-4-(2- amples 1 through 15 herein, the following related com diethylaminoethylamino) - 1 - naphthylazol - 4 - methyl 40 pounds can be prepared, starting from the appropriate 10-thiaxanthenone, of formula, substituted 1-naphthylamine and aminocinnoline, amino pyrazine, aminonaphthinidazole, aminopyridazine, and NH(CH2)N(CH) aminobenzocinnoline compound: 2-[4-(2-diethylaminoethylamino)-1-naphthylazo-3- 45 methylpyrazine. 6-4-(4-diethylamino-1-methylpentylamino)-1- naphthylazol-cinnoline. 4-methyl-8-4-octahydro-1H-quinolizin-1-yl-methyl -N g amino)-1-naphthylazol-cinnoline. /N 50 1-4-(6-chloro-4-pyridazinylazo)-1-naphthylamino-2- methyl-3-dipropylamino-2-propanol. 3-4-(2-diethylaminoethylamino)-1-naphthylazol Ns/ benzoccinnoline. 3-4-(5-diethylamino-1-methylpentylamino)-1- Es 55 naphthylazol-6-methylpyridazine. 2-4-2-(3-isogranatanin-3-yl)-ethylamino)-1- Utilizing the preparative methods described under Ex naphthylazo-pyrazine. amples 1 through 15 herein, the following related com 1-4-(1-methyl-3-piperidylmethylamino)-1-naphthylazo pounds can be prepared, starting from the appropriate benzoccinnoline. substituted 1-naphthylamine and aminothiaxanthene, 60 4-4-(benzoccinnolin-2-ylazo)-1-naphthylamino]-1- aminoxanthene, aminobenzopyran, aminocoumarin, or diethylamino-2-butanol. aminoflavone compound: 3-(4-[2-(4-dimethylaminopiperidino)-ethylamino)-1- 1-(2-diethylaminoethylamino)-4-(4-(2-diethylamino naphthylazo-2-pyrazinecarboxylic acid. ethylamino)-1-naphthylazo)-10-thiaxanthenone. 65 5-[4-(2-diethylaminoethylamino)-1-naphthylazol-2- 1-4-(2-4-(1-methyl-4-piperidyl)-piperidino)-ethyl methyl-1H-naphth-1,2]imidazole. amino-1-naphthylazo)-4-methyl-9-xanthenone. 6-methyl-2-phenyl-4-(4-(2-[2-(piperidinomethyl)- 7-4-(2-diethylaminoethylamino)-6-methoxy-1-naphthyl piperidinol-ethylamino)-1-naphthylazo-3 (2H)- azol-2-oxo-2H-1-benzopyran-3-carboxylic acid. pyridazinone. 1-2-4-(4-methyl-1-thiaxanthenylazo)-1- 70 N-allyl-N-ethyl-N-1-naphthylethylenediamine, B.P. naphthylamino-ethyl-piperidine. 147-148 C./0.07 mm., nd 1.5941, employed as a start 6-4-(2-diethylaminoethylamino)-1-naphthylazol ing material in the above procedure, is prepared from coumarin. N-(2-bromoethyl)-1-naphthylamine, hydrobromide, and 6-4-2-[(2-hydroxyethyl)methylamino-ethylamino}- allyethylamine according to the procedure described un 1-naphthylazo-flavone. 75 der Example 3 herein for the preparation of 1,1-diiso 3,139,421 59 60 propyl-4-methyl-7-(1-naphthyl)-diethylenetriamine. The drops of ethanolic hydrogen chloride gives the desired other intermediate 1-naphthylamines employed herein can 1-methyl-2-(2-[4-(3 - pyridylazo) - 1 - naphthylamino be prepared from the appropriate 1-naphthol or 1-napthyl ethyl-piperidine, trihydrochloride, of formula, amine precursors according to the procedures described under Examples 1 through 15. Example 50 2-amino-3-nitro-5-acetylthiophene (3.72 g., 0.02 mole) is diazotized and coupled into 4.84 g. (0.02 mole) of N isopropyl-N-methyl-N'-1-naphthylethylenediamine accord NHCHCH ing to the procedure described under Example 11 hereinfor O N the preparation of 1-(2-4-(2-thiazolylazo)-1-naphthyl amino]-ethyl-piperidine. Crystallization of the crude dye from an acetonitrile-water mixture gives the desired 5-(4-2-isopropylmethylamino)-ethylamino - 1 - napthyl azo-4-nitro-2-thienyl methyl ketone, of formula, 5

NH(CH)NCH(CH3)(H, 20 as a reddish-purple solid. Utilizing the prepared methods described under Ex NO-- amples 1 through 15 herein, the following related com pounds can be prepared, starting from the appropriate 25 substituted 1-naphthylamine and aminonitrogen hetero Joel, cyclic compound: Utilizing the preparative methods described under Ex Octahydro-2-(2-4-(3-pyridylazo) - 1 - naphthylaminol amples 1 through 15 herein, the following related com ethyl)-1H-pyrido-I1.2-c-pyrimidine. pounds can be prepared, starting from the appropriate 5-4-(4-diethylaminotetrahydrofurfurylamino)-1-naph substituted naphthylamine precursor and amino or hy 30 thylazo)-2,4-dimethylpyrimidine. droxythiophene compound: 5-ethyl-2-(2-piperidinoethyl)-1-(2-4-(3-pyridylazo)-1- 5-ethyl-2-methyl-1-(2-4-(3-nitro-5-trifluoromethyl-2- naphtylamino-ethylpiperidine. thienylazo)-1-naphthylamino-ethyl-piperidine. 5-(4-(2-3-(1-hydroxyethyl)piperidino-ethylamino-1- N,N-diethyl-2,2-dimethyl-N' - 4-(3,5-bis(methylsulfon 35 naphthylazo-6-methyl-2,3,4-pyridinetricarboxylic acid. yl)-2-thienylazo)-1-naphthyl-1,3-propanediamine. 5-(4-(2-((2-diethylaminoethyl)-(1-methyl-2-pyrrolidin N'-[4-(5-benzoyl-3-nitro-2-thienylazo)-1-naphthyl yl)-methylamino-ethylamino-1-naphthylazo-2- N',N'-diethylethylene-diamine. methoxypyridine. N'-[4-(5-amino-2-thienylazo)-1-naphthyl-N,N-di Octahydro-2-(2-4-(3-pyridylazo)-1-naphthylaminol ethylethylenediamine. 40 ethyl-2H-pyrido-1,2]pyrazine. 5-I4-(1-methyl-2-pyrrolidinylmethylamino)-1-naph 1-[4-(6-ethoxy-2-pyridylazo)-1-naphthylaminol thylazo)-2-thiophene-sulfonic acid. methyl 3-octahydro-1H-quinolizine. N'-[4-(5-acetamido-2-thienylazo)-1-naphthyl-N,N-di 1-1 (4-(6-butoxy-3-pyridylazo)-1-naphthylaminol ethylethylenediamine. methyl)-cyclohexylmethyl 3-piperidine. 1-2-[4-(5-ethylsulfonyl-3-nitro-2-thienylazo)-1-naph 45 2,6-dihydroxy-3-(4-3-methyl 3-methylthio)-propyl thylamino-ethyl)-3-piperidinol. amino-propylamino-1-naphthylazo-4-pyridinecar 2-4-(2-diethylaminoethylamino)-1-naphthylazol-4,5- boxylic acid, methyl ester, dihydro-3 (2H)-thiophenone, 1-oxide. 2-2-(4-(5-(aminomethyl)-4-(methoxymethyl)-2-methyl 5-[4-(2-diethylaminoethylamino)-1-naphthylazol-2- 3-pyridylazo)-1-naphthylaminoethyly}-octahydro-1H thiophenol. 50 isoquinoline. 1,1-dimethyl-2-4-(5-phenyl-3-thienylazo)-1-naphthyl)- 5-(4-(2-[(2-hydroxyethyl) (2-piperidinoethyl)aminol 1,2-propanediamine. ethylamino-1-naphthylazo)-2,6-dihydroxy-4-pyrim 5-(4-(4-diethylamino-1-methylbutylamino)-1-naphthyl idinesulfonic acid. azol-2-thiophenecarboxylic acid, ethyl ester. 2,2,6,6-tetramethyl-4-(3-piperidinopropoxy)-1-3-4- 5-(42-ethyl (3-hydroxypropyl)aminol-ethylamino)-1- 55 (3-pyridylazo)-1-naphthylamino-propyl-piperidine. naphthylazo)-2-thiophenearsonic acid. 1,2,2,5,5-pentamethyl-4-(2-4-(3-pyridylazo)-1- N-isoproypl - N-methyl-N'-1-naphthylethylenediamine, naphthylamino-ethyl)-homopiperazine. B.P. 131-132 C./0.1 mm. n25 1.5909, employed as a 3-methoxy-6-4-(2-(2-(2-morpholinoethyl)-piperidino starting material in the above preparation, is prepared ethylamino-1-naphthylazo-pyridazine. from 1-naphthylamine and 2-(isopropylmethylamino)- 60 1-butyl-3-(6-4-(1-ethyl-2-piperidylmethyl)-aminol-1- ethyl chloride, hydrochloride, according to the procedure naphthylazo-3-pyridylsulfonyl)-urea. outlined under Example 1 for the preparation of 1-(2-di 2-benzyl-1-(2-diethylaminoethyl)-5-4-2-(2,5-dimethyl ethylaminoethylamino)-naphthalene. The other substi 1-pyrrolidinyl)-ethylamino-1-naphthylazo-benz tuted 1-naphthylamines employed herein are prepared ac imidazole. cording to the procedures described under Examples 1 65 1-Methyl-2-[2-(1-naphthylamino) - ethyl - piperidine, through 15. B.P. 198-199 C./1.3 mm., employed as a starting ma Example 51 terial in the above procedure, is prepared from 1-naph thylamine and 2-(2-chloroethyl)-1-methylpiperidine ac 3-aminopyridine (4.7 g., 0.05 mole) is diazotized and cording to the procedure outlined under Example 44 here coupled into 13.4 g. (0.05 mole) of 1-methyl-2-1-naph 70 in for the preparation of N,N-diethyl-2-methyl-N'-1- thylamino)-ethyl-piperidine according to the procedure naphthyl-1,3-propanediamine. The other intermediate 1 outlined under Example 6 herein for the preparation of naphthylamine intermediates employed herein can be pre 1-diethylamino-3-4-(3-pyridylazo) - 1 - naphthylamino pared from the appropriate 1-naphthylamine or 1-naph 2-propanol, trihydrochloride. Crystallization of the crude thol compound according to the procedure described dye from a 2-propanol-ether mixture containing a few 75 under Examples 1 through 15. 3,139,421 6. 62 Example 52 ing to the procedures described under Examples 1 through 15. 2-aminothiazole (5.0 g., 0.05 mole) is diazotized and Example 53 coupled into 14.1 g (0.05 mole) of 1-[2-(1-naphthyl amino)-ethyl]-4-methylhomopiperazine according to the 6-aminoindazole (13.3 g., 0.1 mole) is diazotized and procedure outlined under Example 11 herein for the 5 coupled into 32.5 g. (0.1 mole) of 2-(2-dimethylamino preparation of 1-(2-[4-(2-thiazolylazo) - 1 - naphthyl ethyl)-1-2-(1-naphthylamino)-ethyl)-piperidine accord amino)-ethyl}-piperidine. Crystallization of the crude ing to the procedure outlined under Example 3 herein dye from a 2-propanol-water mixture gives the desired for the preparation of 5-4-(2-((2-diisopropylaminoeth 1-2-4-(2- thiazolylazo) - 1 - naphthylamino - ethyl)-4- yl)-methylamino - ethylamino-1-naphthylazo-indazole. O Crystallization of the crude dye from 2-propanol gives methylhomopiperazine, of formula the desired 6-4-2-[2-(2-dimethylaminoethyl)-piperi dino-ethylamino-1-naphthylazo-indazole, of formula, 15 NHCH). X 20 HCHN (CH) as brilliant green crystals. Utilizing the preparative methods described under Ex 25 amples 1 through 15 herein, the following related com pounds can be prepared, starting from the appropriate substituted 1-naphthylamine and aminoheterocyclic com pound: 1-2-(5-ethyl-1-(2-[4-(2-thiazolylazo)-1-naphthylaminol 30 ethyl)-2-piperidyl}-ethyl)-hexahydroindoline. 2-2-[4-(5-benzothiazolylazo)-1-naphthylaminol-ethyl)- as orange-red crystals. O octahydro-1H-pyrido(1,2-c-pyrimidine. Utilizing the preparative methods described under Ex 6-(methylsulfonyl)-2-4-(tetrahydro-4-piperidinofurfur amples 1 through 15 herein, the following related com yl)amino]-1-naphthylazo-benzothiazole. 35 pounds can be prepared, starting from the appropriate sub 2-4-(2-3-(1-hydroxyethyl)-piperidino-ethylamino)-1- stituted 1-naphthylamine and aminonitrogenheterocyclic naphthylazo)-6-benzothiazoleethanol. compound: 2-(2-4-2-(1-methyl-2-pyrrolidinylmethyl) (3-dimethyl 6-4-2-(2,6-dimethylmorpholino)-ethylamino]-1-naph aminopropyl)-amino-ethylamino-1-naphthylazo)-5- 40 thylazo:2,3-diphenylindole. thiazolyl-pyridine. 3,5-dimethyl-4-2-[4-(3-pyridylazo)-1-naphthylaminol 2-(2-[4-(5-benzothiazolylazo)-1-naphthylaminol-ethyl)- ethyl-morpholine. 2H-pyrido1,2)pyrazine. Octahydro-9a-(methyl-2-[4-(3-pyridylazo)-1-naphthyl 5-(4-((octahydro-1H-quinolizin-1-ylmethyl)amino]1- amino-ethyl)amino-9ah-quinolizine. naphthylazo)-2,1,3-benzothiadiazole. 3-(4-(2-bis(2-methylallyl)-amino]-ethylamino-1-naph 5-(4-1-(1-pyrrollidinylmethyl)-cyclohexylamino)-1- 45 thylazo-pyridine. naphthylazo-1,2-benzisothiazole. 3-(4-(2-dicyclopentylaminoethylamino)-1-naphthylazol 2-4-2-ethyl (2-(ethylthio)-ethyl)-amino-ethylamino as-triazine. 1-naphthylazo)-4-(butylsulfonyl)-5-nitrothiazole. 6-4-(1-methyl-2-pyrrollidinylmethyl)-amino)-1-naph Octahydro-2-(2-4-6-(methylsulfonyl)-2-benzothiazolyl thylazo:2-p-tolyl-as-triazine-3,5(2H,4H)-dione. azo]-1-naphthylamino-ethyl)-1H-isoquinoline. 50 5-4-(2-diethylaminocyclohexylamino)-1-naphthylazo)-6- 2-(2-diethylaminoethyl)-2-(4-4-(methylsulfonyl)-5- methyl-3,4-pyridinedimethanol. nitro-2-thiazolylazo]-1-naphthylamino-ethylamino 3-4-(1-methyl-3-pyrrollidinylmethyl)amino]-1-naphthyl ethanol. azo-1,2,4-benzotriazine. 4-(2-diethylaminoethoxy)-2,2,6,6-tetramethyl-1-3-4-(5- 55 2-(2-dimethylaminoethyl) - 1 - 2 - (1 - naphthylamino nitro-2-thiazolylazo)-1-naphthylaminol-propyl)-piperi ethyl)-piperidine, B.P. 170-171° C./0.07 mm., nip25 dine. 1.5875, employed as a starting material in the above pro 4-2-4-(4,9-dioxo-5-thiophanthrenylazo)-1-naphthyl cedure, is prepared from N-(2-bromoethyl)-1-naphthyl aminol-ethyl)-1-ethyl-2,2,5,5-tetramethylhomopipera amine, hydrobromide, and 2-(2-dimethylaminoethyl)- Z11e. piperidine according to the procedure described under 4-4-2-2-2-(1-pyrrolidinyl)-ethylpiperidino-ethyl 60 Example 3 herein for the preparation of 1,1-diisopropyl amino-1-naphthylazo)-2,1,3-benzothiadiazole. 4 - methyl-7-(1-naphthyl)-diethylenetriamine. The other 4-amino-7-4-(1-ethyl-2-pyrrolidinylmethyl)-amino]-1- intermediate 1-naphthylamines employed herein can be naphthylazo)-2,1,3-benzothiadiazole. prepared from the appropriate 1-naphthol or 1-naphthyl 2-4-2-(2,6-dimethylpiperidino)-ethylamino]-1-naphthyl 65 amine precursors according to the procedures described azo-dibenzo-Ib,f(1,4,5thiadiazepine, 11,11-dioxide. under Examples 1 through 15. 1-2-(1 - naphthylamino)-ethyl]-4-methylhomopiperazine, Example 54 employed as an intermediate in the above procedure, is prepared from N-(2-bromoethyl)-1-naphthylamine, hy 8-aminoquinoline (7.2 g., 0.05 mole) is diazotized and drobromide, and 1-methylhomopiperazine according to 70 coupled into 12.8 g. (0.05 mole) of 1-2-(1-naphthyl the procedure described under Example 3 herein for the amino)-ethyl-piperazine according to the method out preparation of 1,1-diisopropyl-4-methyl-7-(1-naphthyl)- lined under Example 4 herein for the preparation of 8-4- diethylenetriamine. The other intermediate 1-naphthyl (3-diethylamino - 2,2-dimethylpropylamino)-1-naphthyl amines employed herein can be prepared from the appro azol-5,6-dimethoxyquinoline, trihydrochloride. Purifica priate 1-naphthol or 1-naphthylamine precursors accord 75 tion of the crude dye from 2-propanol gives the desired 3,139,421 63 64 8-{4-2-(1-piperazinyl) - ethylaminol - 1 - naphthylazo azo)-1-naphthylamino]-ethyl)-1-azaspiro[4,5-decane, of quinoline, trihydrochloride, of formula, formula,

M N NH(CH)N NH N-1

3IC 10 N=

N N 5 as red crystals. Utilizing the preparative methods described under Ex amples 1 through 15 herein, the following related com as a hydrated deep maroon crystalline solid, M.P. 210 C. pounds can be prepared, starting from the appropriate (dec.). substituted 1-naphthylamine and hydroxy or aminohetero Utilizing the preparative methods described under Ex 20 cyclic compound: amples 1 through 15 herein, the following related com 2-(2-dimethylaminoethyl)-5-ethyl-1-(2-[4-(5-phenyl-2- pounds can be prepared, starting from the appropriate thienylazo)-1-naphthylaminol-ethyl)-piperidine. substituted 1-naphthylamine and aminonitrogenheterocy 1,2,3,4-tetrahydro-6-methyl-9-4-2-(octahydro-1H clic compound: 25 pyrido 1,2-c-pyrimidin-2-yl)-ethylamino]-1-naph thylazo)-10-thiaxanthenone. 1-methyl-5-4-(1-methyl-2-piperidinoethyl)-amino)-1-naphthylazo-indole. 4-dimethylaminotetrahydro-2-(1-[4-(4-phenyl-2- 6-4-(2-diidopropylamino-1-methylethyl)amino)-1- thienylazo) 1-naphthylaminol-ethyl)-furan. naphthylazo-8-methoxy-4,5-dimethyl-2(1H) quinolone. 1-2-[4-(6-chromanylazo)-1-naphthylaminol-ethyl)-a-methyl-3-piperidine-methanol. 6-4-2-(hexahydro-1-azepinyl)-1-methylethylaminol-1-naphthylazo-1,4-dihydro-2-methyl-4-oxo-3-quinoline 30 9-4-2-(3-dimethylaminopropyl)-(1-methyl-3- carboxylic acid. tetrahydro-6-methyl-10-thiaxanthenone,piperidyl)aminol-ethylamino-1-naphthylazo-1,2,3,4- 9-(2-diethylaminoethyl)-3-(4-1-methyl-2-(1-pyrrolidinyl)ethylamino-1-naphthylazocarbazole. 8-methyl-5-4-2-(octahydro-2H-pyrido-1,2]pyrazin-2- 3-4-(2-((2-(2-diethylaminoethyl)ethylaminol-ethyl)- 35 yl)-ethylamino]-1-naphthylazo-thiachromone. ethylamino-ethylamino-1-naphthylazo-quinoline. Octahydro-3-(4-3-(methylsulfonyl)-5-nitro-2- 5-(4-2-(3-azabicyclo[3.3.1) nonan-3-yl)-ethylaminol-1- thienylazo)-1-naphthylaminomethyl)-1H-quinolizine. naphthylazo)-6-methylcinchomeronic acid, dimethyl 5-(4-1-(diisopropylaminomethyl)-cyclohexylaminol-1- ester. naphthylazo-8-methyl-4-thiachromanone. . 6-4-2-(diethylaminomethyl)-cyclohexylamino]-1- 40 4-2-4-(6-chromanylazo)-1-naphthylaminoethyl napthylazo-1,4-dihydro-2,3-quinoxalinedione. thiamorpholine. 6-4-2-(dimethylaminomethyl)-cyclopentylamino]-1- 8-methyl-5-4-2-(octahydro-2(1H)-isoquinolyl)-ethylamino]-1-naphthylazo-thiachromone. 3-4-2-(dimethylaminomethyl)-cycloheptylaminol-1-naphthylazo)-1,3-dihydro-2,4-quinazolinedione. 1-4-(2-(2-dibutylaminoethyl)-(2-hydroxyethyl)amino naphthylazo-pyridine. 45 ethylamino-1-naphthylazo)-4-methyl-9-xanthenone. 6-4-3-(diethylaminomethyl)-1-methyl-4-piperidyla 1-4-(2-4-(2-diethylaminoethylamino)methylpiperidino-ethylamino-1-naphthylazo)-4- 2,2,6,6-tetra mino]-1-naphthylazo-4-phenyl-2(1H)-quinolone. methyl-10-thiaxanthenone. 1,2,3,5,6-pentamethyl-4-(2-4-(3-pyridylazo)-1-napththylaminol-ethyl-piperazine. 1,2,2,5,5-pentamethyl-4-(2-4-5-(methylsulfonyl)-3- 2-(2-4-(2-[4-(3-pyridylazo-1-naphthylamino-ethyl)-1- 50 nitro-2-thienylazol-1-naphthylamino-ethyl-homo piperazinyl-ethoxy-ethanol. piperazine. 6-4-2-(1-ethyl-4-piperidyl)-ethylamino-1-naphthyl 1,2,3,4-tetrahydro-6-methyl-9-4-2-2-(2-piperidino azo-2,4(1H,3H)-quinazolinedione. ethyl)-piperidino)-ethylamino-1-naphthylazo)- 1-pentyl-4-3-4-(3-pyridylazo)-1-naphthylaminol benzo[5,6thiapyrano3,2-clthiapyran-10-one. propyl-piperazine. 55 5-(4-2-(1-butyl-2-piperidyl)-ethylamino]-1-naph 1-2-(1-naphthylamino)-ethyl-piperazine, B.P. 170 thylazo)-N-ethyl-4-nitro-2-thiophenesulfonamide. 173° C./0.25 mm., n5 1.7023, employed as an inter 1-2-(4-3,5-bis(methylsulfonyl)-2-thienylazo-1-naph mediate in the above procedure, is prepared from 1 thylaminoethyl)-2,4,6-trimethylpiperidine. naphthol and 1-(2-aminoethyl)-piperazine according to 1-2-(1-naphthylamino)-ethyl-1-azaspiro[4.5 - decane, the procedure outlined under Example 8 herein for the 60 employed as an intermediate in the above procedure, is preparation of 1-(3-dimethylamino-propylamino)-naph prepared from N-(2-bromoethyl)-1-naphthylamine, hy thalene. The other intermediate 1-naphthylamines em drobromide, and 1-azaspiro[4,5)-decane according to the ployed herein can be prepared from the appropriate 1 procedure described under Example 3 herein for the prep naphthol or 1-naphthylamine precursors according to the aration of 1,1-diisopropyl-4-methyl-7-(1-naphthyl)-di procedures described under Examples 1 through 15. 65 ethylenetriamine. The other intermediate 1-naphthyl amines employed herein can be prepared from the appro Example 55 priate 1-naphthol or 1-naphthylamine precursors accord 3-aminodibenzofuran (18.3 g., 0.1 mole) is diazotized ing to the procedures described under Examples 1 through and coupled into 30.8 g. (0.1 mole) of 1-2-(1-naphthyl 15. amino)-ethyl)-1-azaspiro 4.5-decane according to the 70 Example 56 procedure described under Example 1 herein for the preparation of 5-4-(2-diethylaminoethylamino)-1-naph (4,6-disulfo-1,3,2-benzodioxastibiol-2-yloxy)-1-phenol-3,To an aqueous solution of 2.30 g. (0.0030 mole) of 2 thylazol-uracil. Crystallization of the crude dye from 5-disulfonic acid, pentasodium salt, heptahydrate there 2-propanol gives the desired 1-2-[4-(3-dibenzofuranyl 75 is added an aqueous solution of 2.57 g. (0.0050 mole) of 3,139,421 65 66 3 - 4 - (2 - diethylaminoethylamino) - 1 - naphthylazol sisting of lower alkyl, lower hydroxyalkyl, lower alkoxy pyridine, trihydrochloride, trihydrate. After stirring for alkyl and lower dialkylaminoalkyl; and a few minutes the supernatent solution is removed from HET is a heterocyclic radical selected from the group the material which separates. This residue is washed with consisting of methanol, powdered, and dried in vacuo. This material, M.P. 215 C. (dec.), is a salt which contains the above pyrimidyl pyrrolopyridinyl pyridine compound and the above disulfonic acid in a pyridyl pyridobenzimidazolyl molar ratio of about five to four. indazolyl benzothiazolyl We claim: quinolyl naphthothiazolyl 1. A member selected from the group consisting of a O isoquinolyl tetranaphthoxazolyl free base of formula dibenzofuryl carbazolyl furyl tetrahydrocarbazolyl benzofuryl indolyl tetrahydrodibenzofuryl pyrrolyl benzimidazolyl thianthrenyl 15 naphthimidazolyl phenoxathiinyl quinazolinyl methylenedioxyphenyl quinoxalinyl benzodioxanyl thiazolyl benzoxathiolyl 20 pyrazolyl benzothiadiazolyl N=N-HET pyrazolinyl benzisothiazolyl phthalazinyl benzisothiazolinyl benzophthalazine thienopyridyl benzothiazinyl benzoxazolinyl and addition salts thereof with pharmaceutically accepta dibenzothiazinyl benzoxazolyl ble acids; wherein 25 phenothiazinyl napthoxazolinyl R represents a member selected from the group consist thianaphthenyl acridinyl ing of hydrogen, chloro, bromo, lower alkyl and lower dibenzothienyl acridanyl alkoxy; benzotriazolyl thiadiazolyl Y represents a member selected from the group con triazolyl oxadiazolyl sisting of 30 triazolinyl imidazolyl tetrazolyl isoxazolyl benzoquinolyl thiaxanthenyl phenanthridinyl xanthenyl dihydronaphthoxazinyl benzopyranyl 35 tetrahydroquinazolinyl pyrazinyl tetrahydroquinolyl pyridazinyl indolinyl cinnolinyl and dihydrobenzoxazinyl benzocinnolinyl dihydroquinolyl naphthimidazolyl 40 tetrahydroquinoxalinyl thienyl CH) tetrahydrobenzoquinolyl dihydrothienyl -(CH2)f-CH N-R dibenzothiadiazepinyl thiophanthrenyl CEI), benzothiapyranopyridyl triazinyl phenazinyl benzotriazinyl 45 phenazinium chloride dihydroquinoxalinyl wherein A represents a member selected from the group phenazonium hydroxide dihydroquinazolinyi consisting of alkylene containing between 2 and 8 carbon inner salt chromonyl atoms inclusive, and alkylene containing more than 2 and phenazathionium chloride thiachromonyl and less then 7 carbon atoms in which one of the methylene phenazoxonium chloride benzothiapyranothiapyranyl groups not attached to the nitrogen atoms of 50 isophenoxazinyl -NH-A-NC and derivatives of said heterocyclic radicals containing at least one substituent of the group consisting of keto, hy is replaced by a member selected from the group consist 55 droxy, lower alkyl, trifluoromethyl, phenyl, chlorophenyl, ing of -O-, -S-, FCHOH, FCOH(lower alkyl), lower alkoxy, nitro, amino, imino, lower hydroxyalkyl, FN(lower alkyl) and FCH(lower dialkylaminoalkyl); lower aminoalkyl, chloro, bromo, lower dialkylamino R1 and R2 each represent a member selected from the alkyl, lower alkylamino, lower dialkylaminopiperidino, group consisting of (a) , alkyl, alkoxyalkyl, hydroxyalkyl lower carbalkoxy, lower alkyl carbamate ester, phenoxy, and cycloalkyl each containing fewer than 7 carbon atoms 60 phenylazo, anilino, pyridyl, mercapto, lower alkylmer and (b) alkyl, methallyl, and lower dialkylaminoalkyl capto, phenylmercapto, N-oxide, benzyl, tolyl, styryl, ben containing 3 to 7 carbon atoms inclusive, and further Zoyl, acetyl, trifluoroacetyl, acetamido, arsonic acid, sul members wherein-NRR2 represents a heterocyclic radi fo, carboxy, thio, sulfonamido, sulfonyl, imidazolinyl and cal selected from the group consisting of heterocyclic carboxamidine, radicals containing fewer than 10 carbon atoms con 65 2. 5 - 4-(2-diethylaminoethylamino)-1-naphthylazo taining at least one hetero atom selected from the group uracil. consisting of oxygen, nitrogen and sulfur and derivatives 3, 1-diethylamino-3-(4-(3-pyridylazo) - 1 - naphthyl thereof containing at least one nuclear substituent selected amino)-2-propanol. from the group consisting of lower alkyl, lower hydroxy 4. 1-(2-4-(2-thiazolylazo)-1-naphthylamino - ethyl) E: hydroxy, lower alkoxy, and lower dialkylamino piperidine. alkyl; 70 5. 4-4-(2-diethylaminoethylamino) - 7 - methoxy-1- f represents an integer from 0 to 3 inclusive; g and h naphthylazol-2,3-dimethyl-1-phenyl-3-pyrazoline-5-one. represent integers such that the sum of g and h equals an 6, 6-4-(2-dimethylamino - 1 - methylethylamino)-1- integer from 3 to 4; naphthylazol-1 H-benzotriazole. R3 represents a member selected from the group con 75 (References on following page) 3,139,421 67 68 References Cited in the file of this patent FOREIGN PATENTS UNITED STATES PATENTS 442,190 Great Britain ------Feb. 4, 1936 1,925,434 Clingestein et al. ------Sept. 5, 1933 2,022,921 Mietzsch et al. ------Dec. 3, 1935 5 OTHER REFERENCES 2,068,353 Schneiderwirth ------Jan. 19, 1937 Dickey et al.: "Ind. and Eng. Chem.' vol. 46, October 2,307,650 Tisza et al. ------Jan. 5, 1943 1954, pp. 2213-2220. 2,430,439 Winnek et al. ------Nov. 5, 1947 Conant and Blatt: "The Chem. of Org. Comp,” 4 ed. 2,561,948 Rawlins ------July 24, 1951 (1956), pp. 183-184, The Macmillian Co., New York. 2,980,665 Langley et al. ------Apr. 18, 1961 UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3, 139, 42l June 30, 1964 Edward F. Elslager et al. It is hereby certified that error appears in the above numbered pat ent requiring correction and that the said Letters Patent should read as corrected below. Column 8 line 23, for "-naphthylazol" read - - -naphthylazor --; line 29, for '-naphthaylazo" read -- naphthylazo --; column 9 line 7, for "-dimethyl-" read -- -diethyl- --; lines 34 and 35 for "-naphthylazol" read -- -naphthylazo --; column 15 line 25, for "-(diethylaminoethyl)-' read - - -(diethylaminomethyl)- --; column 17 lines ll to 22 the formula Should appear as shown below instead of as in the patent :

NHCCH)3N O

H column 23 line 69 for '-(3-dim ethlaminopropylamino) -' read -- - (3-dimethylaminopropylamino) - - -; column 25 line 20 for "napthyl)-" read -- naphthyl) - - -; column 27 line 52 for "3-5-" read -- 3-4-(5- - - ; line 53 for "-propylamino" read -- -propylimino --; same column 27 line 72 for "5" read -- 3 --; column 3O lines 29 and 3O, for "-naphthylene diamine" read - - -naphthylethylene diamine --; column 31 lines 46 to 55, the formula should appear as shown below instead of as in the patent :

3, 139, 421 NHCCH)N(CH3)2 -1 a

to V / OH same column 31 line 64 for "-piperilino" read -- pipe ridino --; column 32 line 66 for '-(2-diethylaminoethylamin) -" read - - - (2-diethylaminoethylamino) - - -; column 33 line 39 for "l3O-l23° C. " read -- 13O-132° C. --; line 53 for "2-2." read -- 2-(2- --; same column 33 line 7O for "naphthylamine" read -- naphthylamino --; column 35 lines 19 to 28, the formula should appear as shown below instead of as in the patent : ...: NHCCH)N(CHCCH) all-cal-N 1SN Sarae column 35 line 6O for "-(diethylaminoethyl)-" read - - - (diethylaminomethyl) - - -; line 68 for "l. 57, 82" read -- 5782 --; column 37 line l6 for '-pyrazol' read ---, -pyrazolol --; column 40 line 8, for "-(3-diethylamino propy oxy) -" read - - - (3-diethylaminopropoxy) - --; line 20 for ": -naphy ithylamines" read -- l-naphthylamines -- ; line 3l for 'inadzole" read - - -indazole --; line 6l for "napthylazo" read -- naph. hylazo --; line 67 for "diime thylaminopyridine" read -- dime tiny laminopy ridine -; Same column 4O line 7O for "-ame tamido-" read - - -acetamido- - -; column 4l line 9, for "-pipe ridi no" read - - -pipe ridinol --; column 42 line 47 for "-raph tinto" read - - -naphtho --; line 5O, for "3-diethylamino prop y" read -- 3-diethylaminopropyl -- ; column 43 line 32, for '-2 2-dimethylprop lyamino) -" read - - -2 2-dimethylpropyl amino) - - - ; line 36 for "2-4-2-" read -- 2-4-(2- - -; same column 43 line 45, for "i-3 2-4-" read -- l-2-4- --; column 44 line 4l, for "3--5-" read -- 3-5- - -; line 50 for '-(2-methylally) -" read - - -(2-methylallyl) - - -; column 46, line S la to 29, the formula should appear as shown below instead of as in the patent :

s 3, 139, 42l

N N N2 OCH3 column 47 line 73 for "N-diethylethylene diamine" read -- N,N-diethylethylenediamine --; column 5l lines 10 to 19 the formula should appear as shown below instead of as in the patent :

NN same column 5l line 69 for "l2-l-" read -- 1:2-(l- - -; column 54, line 4O for "-(2-cyclohexylmethylamino)-" read -- -(cyclo hexylmethylamino) - - -; column 55 line 7, for "-oxo2-" read -- -oxo-2- --; line 29 for "nitrate" read -- nitrite --; same column 55 line 57 for "wash" read -- washed --; column 59 line 33 for "-trifluoromethy4-" read - - -trifluoroacetyl- -- line 7O for "-2-Il-" read - - -2-[2-(l- --; column 60 line 22, for "prepared" read -- preparative --; line 33 for "naphtyl amino-" read -- naphthylamino - - -; same column 6O line 49, for "ethyly" read -- -ethyl --. Signed and sealed this 23rd day of March 1965.

(SEAL) At test : ERNEST W. SWIDER EDWARD J. BRENNER At testing Officer Commissioner of Patents