M/S. Ishanga Life Science Pvt. Ltd. ANNEXURE- I

M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

ANNEXURE- I

PROPOSED TERMS OF REFERENCE

As per standard ToR of organic manufacturing sector issued by MoEF&CC.

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 1 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

ANNEXURE-II

LIST OF DIRECTORS

Sr. No. Name of Directors Residential Address Contact no.

1. Mr. Ramlal Maru 33,34-Narmada Nagar, Kanjari Road, Halol 9825033071

2. Mr. Jigar Maru 33,34-Narmada Nagar, Kanjari Road, Halol 9722221941

3. Ms. Tanvi Tank C-25/26, Uma society, Kanjari Road, Halol 9619680061

4. Ms. Avani Bhattacharya B-302, Surya Kiran Society, Charwada Road, Vapi 7715086528

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 2 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

ANNEXURE-III

PLAN LAY OUT

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar . 3 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

ANNEXURE- IV

LIST OF PRODUCTS WITH PRODUCTION CAPACITY

Sr. Capacity End usage in mfg Name of Products CAS No. No. (MT/Month) following bulk drug

1 5-Nitrofurfural diacetate 92-55-7 3 Nitrofurantoin

2 1 amino hydantoin 2827-56-57 3 Nitrofurantoin Phosphoryl choline chloride, calcium 3 72556-74-2 7 Citicoline salt 4 Citicoline (CTS) tech 33818-15-4 5 Citicoline

2-(4-Aminopentyl (ethyl) amino) Hydroxy chloroquin 5 69559-11-13 10 ethanol sulphate

Solesenacin & 6 3-Quinuclidinone 3731-38-2 10 pemilin 1-Ethyl-3-(3-Dimethylaminopropyl) Intermediate for 7 25952-53-8 15 Carbodimide Hydrochloride Gliptin Series API Ketoprofen 8 3-(1-Cyanoethyl) Benzoic Acid 5537-71-3 15 intermediate

1-(p-methoxy benzyl)- Dextromethorphan 9 1,2,3,4,5,6,7,8,Octahydro iso quinaline- 30356-07-1 8 hydrobromide S-octa base

Dextromethorphan 10 Dextrometharphin free base 6700-34-1 8 hydrobromide Cis-2-(2,4-Dichloro phenyl)-2-(1H- 1,2,4-triazol-1-yl-methyl)-1,3- 11 67914-86-7 10 Itraconazole dioxolan-4-yl methyl methane sulfonate- cis-2-(2,4-Dichloro phenyl)-2-(1H- 1,2,4-triazol-1-yl-methyl)-1,3- 67914-86-7 12 8 Itraconazole dioxolan-4-yl methyl methane sulfonate - CRUDE Phenyl (1h pyrrole-2-yl)methanone – 13 136116-84 10 Ketorolac tricarboxylate crude (-)-1-[(4-Chlorophenyl)phenylmethyl]- 14 4-[(4-methylphenyl) sulfonyl] 163837-56-7 6 Levocetrizine piperazine

15 p-Chloro benzhydryl piperazine 303-26-4 6 Levocetrizine

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 4 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

Sr. Capacity End usage in mfg Name of Products CAS No. No. (MT/Month) following bulk drug 2,3 pyrridine Benzyle carboxylate 16 151213-40-0 5 Moxyfloxacin Hydrate Chloro compound 3,4-dimethoxy-2-chloro methyl 17 169905-10-6 10 Pentaprozole pyridine

18 pentaprozole sulphide 102625-64-9 10 Pentaprozole

19 Pregabalin (Racemic) 148553-50-8 8 Pregabalin 11-Piperazinyl-dibenzo(b,f) (1,4)- 20 111974-74-4 8 Quetiapine thiazepine hydrochloride 11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1- 21 piperazinyl] dibenzo (b, f) (1, 4) 111974-72-2 8 Quetiapine thiazepine hemifumarate 2-[(4-(3-methoxypropoxy)-3-methyl- 22 2-pyridinyl)methyl]thio]-1H- 117977-21-6 10 Rabeprazole benzimidazole 2-[4-(3-methoxypropoxy)-3-methyl-2- 23 pyridinyl]methyl]sulfinyl]-1H- 117977-21-6 10 Rabeprazole benzimidazole Total ---- 193 ----

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 5 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

ANNEXURE – V

LIST OF RAW MATERIALS WITH CONSUMPTION QUANTITY Sr No Raw Material CAS No. Capacity (MT/Month)

1 Cyclohexane Ethylamine 3399-73-3 7.00

2 Methane sulfonyl chloride 124-63-0 3.58 3 Sodium hydroxide 1310-73-2 7.02

4 1,2,4-Triazole 288-88-0 7.00

5 2,3 pyrridne dicarboxylic acid 89-00-9 6.40 6 2,3-Dimethyl-4-nitropyridine N-oxide 37699-43-7 8.40 7 2-Aminodiphenyl sulphide 1134-94-7 4.70

8 2-Bromo butane 78-76-2 11.10

9 2-chloro ethanol 107-07-3 2.60 10 2-Chloroethoxy ethanol 628-89-7 6.79 11 2-furaldehyde diacetate 92-55-7 61.20 12 2-mercapto benzimidazole 583-39-1 11.40 13 2-Propanone 110-20-3 11.88 14 3-Methoxy Propanol 1589-49-7 5.46

15 104-01-8 7.00 4-[4-[4-(4-methoxy phenyl)-1-acetic acid 4-[4-[4-(4-methoxy phenyl)-1-piperazinyl]phenyl]- 16 74853-07-9 11.10 3H -1,2,4-triazol-3-one 17 5 difluoro methoxy 2 mercapto benzimidazole 64-19-7 10.91

18 Acetic acid (Fresh+ Recovered) 64-19-7 220.14 19 Acetonitrile (Fresh+ Recovered) 75-05-8 254.44

20 Acetic anhydride 108-24-7 86.17 21 Acetone (Fresh+ Recovered) 67-64-1 216.80 22 Activated Carbon 7440-44-0 0.58 23 Aluminium Chloride 7446-70-0 0.24

24 Ammonia formate 540-69-2 0.02

25 Ammonia solution 7664-41-7 11.20 26 Ammonium Sulphate 7783-20-2 9.44 27 Sulfuric acid 7664-93- 7.15 28 Benzoic Acid 65-85-0 34.00

29 Benzyl amine 100-46-9 8.74

30 Benzyl chloride 100-44-7 8.00

31 Bis 2 chloro ethylene hydrochloride 821-48-7 9.48 32 Bromine 7726-95-6 5.08 33 Calcium Carbonate 1317-65-3 10.78 34 Carbon 7440-44-0 36.39 35 Catalyst (DCC) 538-75-0 9.49

36 Caustic Flakes 1310-73-2 72.72

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 6 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal 37 Chloro- 2- Pentanone 5891-21-4 18.20 38 67-66-3 1227.10 Chloroform (Fresh+ Recovered) cis-[(2-bromomethyl)-2-(2,4-dichlorophynyl)-1,3- 39 61397-56-6 20.00 dioxolan -4-yl methyl] benzoate 40 Cyclo hexynyl ether 78917-92-7 5.25 41 Cytidine Monophospahte (CMP ) 67-63-6 7.20 42 Di ethyl Malonate 105-53-3 15.58 43 Di Methyl Carbonate 616-38-6 51.00 44 Di n Propyl amine 142-84-7 565.50 45 Dichloromethane 75-09-2 350.78 46 Diiso propyl ethyl amine 36340-89-3 11.62

47 Dimethyl formamide 68-12-2 62.13

48 Dimethyl Malenate 108-59-8 10.56

49 Dimethyl sulfoxide 67-68-5 44.40 50 Dimethyl sulphide 75-18-3 9.00

51 D-Mandalic acid 611-71-2 6.05

52 DMF 68-12-2 18.92

53 D-tartaric acid 147-71-7 4.00 54 EDC (Fresh+ Recovered) 25952-53-8 124.80 55 Ethanol 64-17-5 50.40

56 Ethyl acetate (Fresh+ Recovered) 141-78-6 212.65

57 Ethyl chloro formate 541-41-3 8.58 58 Ethyl Chloro acetate (Fresh+ Recovered) 105-39-5 286.00 59 Ethyl Cyano acetate 105-56-6 5.98

60 Ethyl Formate 109-94-4 12.75

61 Ethyl Piperidine Carboxylate 1126-09-6 14.30 62 Ethylisothiocynate 542-85-8 14.70

63 Formaldehyde 50-00-0 67.08 64 Fumaric acid 110-17-8 3.40 65 Hcl (Fresh+ Recovered) 7647-01-0 147.25 66 Hydrazine Hydrate 10217-52-4 14.10

67 Hydrobenzoic acid 99-96-7 7.47 68 Hydrobromic acid 10035-10-6 38.27 69 Hydrogen Gas 1333-74-0 46.40 70 Hydrogen peroxide 7722-84-1 7.03 71 Hyflow 61790-53-2 1.66 72 Ice 7789-20-0 23.00 73 IPA 67-63-0 11.68 74 Iso Propyl HCL 51639-49-7 0.60 75 Isovelaraldehyde 590-86-3 4.41 76 L+tartaric acid 526-83-0 15.05 77 Liquod Ammonia 1336-21-6 36.20 M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 7 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal 78 Maltol 118-71-8 9.00 79 MDC (Fresh+ Recovered) 75-09-2 655.27

80 Megnesium acetate 142-72-3 8.80

81 Megnesium oxide 1309-48-4 5.28 82 Methanol (Fresh+ Recovered) 67-56-1 2014.07 83 Methanolic Ammonia 1336-21-6 18.20 84 Methanolic Hcl 7647-01-0 7.20 85 Methyl Chloroacetate 96-34-4 2.21

86 Methylene chloride 75-09-2 49.28 87 Morpholine 110-91-8 10.96 88 N, N-Dimethylaniline 121-69-7 1.66 89 N,N Dimethyl-1,3-Propanediamine 109-55-7 294.00 90 NaoH flakes 1310-73-2 7.70 91 N-Ethyl ethanol amine 110-73-6 22.75 92 n-Heptane 142-82-5 28.20 93 N-Hexane 110-54-3 13.43 94 Nitric acid 7697-37-2 8.85

95 Nitrogen gas 7727-37-9 3.22 96 N-methyl pyrrolidinone 872-50-4 13.58 97 Orgno Copper Catalyst 7440-58-8 0.91 98 Palladium carbon 5/3/7440 1.74

99 Parachloro benzo phenon 134-85-0 10.00 100 Phenylchloroformate 1885-14-9 4.38 101 Phosphorous Oxychloride 10025-87-3 17.34

102 Phosporic acid 7664-38-2 64.80 103 Phosporous pentaoxide 1314-56-3 28.19 104 Piperazine 110-85-0 5.17

105 Pocl3 10025-87-3 42.80 106 Poly phosphoric acid 8017-16-1 22.75 107 Potassium 7440-09-7 9.90 108 Potassium carbonate 584-08-7 72.30 109 Potassium Hydroxide 1310-58-3 14.86 110 Potassium Tert- Butoxide 865-47-4 5.72 111 Propanone - 67-64-1 3.78 112 PTSC 98-59-9 7.83 113 Pyridine 110-86-1 0.89

114 Pyrrole 109-97-7 46.00 115 R-(+) ∞ Phenyl ethyl amine 3886-69-9 5.77 116 Raney Nickel 12003-78-0 7.28 117 Side Chain (Phosporyl Choline chloride) 4826-71-5 18.00 118 Soda ash 497-19-8 26.44 119 Sodium bi carbonate 144-55-8 2.44 120 Sodium carbonate 497-19-8 7.67 M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 8 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal 121 Sodium Cyanide 143-33-9 20.40 122 Sodium Hydroxide 1310-73-2 48.72 123 Sodium Hypochlorite 7681-52-9 82.60 124 Sodium Iodide 7681-82-5 0.58

125 Sodium Methoxide 124-41-4 25.29 126 Sodium mono chloro acetate 3926-62-3 3.96 127 Sodium Sulfate 7757-82-6 16.03 128 Sodium tungaste 13472-45-2 0.22 129 Sodiumhydroxide 1310-73-2 7.03 130 Sulfuric Acid (Fresh+ Recovered) 7664-93-9 336.45 131 TBAB 1643-19-2 1.50

132 Tetrabutylammonium bromide 311-28-4 1.18

133 THF 109-99-9 21.00 134 Thionyl chloride 9/7/7719 13.87 135 Toluene (Fresh+ Recovered) 108-88-3 1779.66

136 Triethyl amine 121-44-8 5.48 137 Urea 57-13-6 10.70 138 Xylene (Fresh+ Recovered) 1330-20-7 364.00

With representative the Product’s raw material consumption is given below:

sr. Quantity Product wise Raw materials CAS No. No. MT/MT MT/Month 1 5-Nitrofurfural diacetate 92-55-7 1.000 3.00 2-furaldehyde diacetate 92-55-7 1.76 5.29 Pyridine 110-86-1 0.59 1.76

Acetic anhydride 108-24-7 5.88 17.65 Sufuric Acid 7664-93-9 2.94 8.82 Nitric acid 7697-37-2 2.94 8.82

Acetic acid 64-19-7 2.94 8.82 Sodium Hydroxide 1310-73-2 0.59 1.76 Total 17.647 52.941

2 1 amino hydantoin 2827-56-57 1.000 3.00 Hydrazine Hydrate 10217-52-4 1.250 3.750 Urea 57-13-6 1.125 3.375 Acetone 67-64-1 15.000 45.000 2-Propanone semicarbazone 110-20-3 0.813 2.438

Sodium Methoxide 124-41-4 0.375 1.125 Methyl Chloroacetate 96-34-4 0.438 1.313 Propanone semiaminohydrantoin 2827-56-7 0.750 2.250 Hcl 7647-01-0 0.188 0.563

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 9 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Total 19.938 59.813

Phosphoryl choline chloride, calcium 3 72556-74-2 1.000 7.00 salt Choline Chloride 67-48-1 1.111 7.778 Phosporyl chloride 4826-71-5 1.444 10.111 Calcium Chloride 10043-52-4 0.556 3.889 Calcium Carbonate 1317-65-3 1.111 7.778 Methanol 67-56-1 3.333 23.333 Total 7.556 52.889

4 Citicoline (CTS) tech 33818-15-4 1.000 5.00 Cytidine Monophospahte (CMP ) 67-63-6 1.429 7.143 Methanol 67-56-1 32.143 160.714 Morpholine 110-91-8 1.143 5.714 DCC (N,N'-Dicyclohexylcarbodiimide) 538-75-0 1.857 9.286 Phosphorul Choline chloride 4826-71-5 3.571 17.857 Methanolic Hcl 7647-01-0 1.429 7.143 IPA 67-63-0 14.286 71.429 Activated Carbon 7440-44-0 0.114 0.571 Sodium Hydroxide 1310-73-2 0.143 0.714 Ethanol 64-17-5 10.000 50.000 Total 66.114 330.571

2-(4-aminopentyl (ethyl) amino)

5 69559-11-13 1.000 20.00 ethanol 5 Chloro 2 pentanone 5891-21-4 0.909 18.182 Xylene (Fresh) 1330-20-7 0.909 18.182 N-Ethyl ethanol amine 110-73-6 1.136 22.727 Orgno Copper Catalyst 7440-58-8 0.045 0.909 Raney Nickel 12003-78-0 0.364 7.273 Methanol 67-56-1 13.636 272.727 Methanolic Ammonia 1336-21-6 0.909 18.182 Hydrogen Gas 1333-74-0 1.818 36.364 Total 19.727 394.545

6 3-Quinuclidinone 3731-38-2 1.000 10.00

Ethyl Piperidine Carboxylate 1126-09-6 1.429 14.29 Toluene (Fresh) 108-88-3 2.857 28.57 Ethyl Chloro acetate 105-39-5 3.071 30.71 Potassium Tert- Butoxide 865-47-4 1.571 15.71 Hcl Acid solution 7647-01-0 1.429 14.29

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 10 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Sulfuric Acid 7664-93-9 0.714 7.14 Sodium hydroxide 1310-73-2 1.786 17.86 Chloroform (Fresh) 67-66-3 11.429 114.29 IPA Hcl 70849-64-8 0.714 7.14 Total 25.00 250.00

1-ethyl-3-(3-dimethylaminopropyl)

7 25952-53-8 1.000 20.00 carbodimide. hydrochloride Ethylisothiocynate 542-85-8 0.732 14.63 Chloroform 67-66-3 14.459 289.17 N,N Dimethyl-1,3-Propanediamine 109-55-7 0.927 18.54 Calcium Carbonate 1317-65-3 0.537 10.73 Potassium Hydroxide 1310-58-3 0.463 9.27 Acetonitrile 75-05-8 12.195 243.90 Hcl (Gas) 7647-01-0 0.244 4.88 Total 29.56 591.12

8 3-(1-cyanoethyl) benzoic acid 5537-71-3 1.000 30.00 Benzoic Acid 65-85-0 1.111 33.33

Formaldehyde 50-00-0 2.000 60.00 Methanol (Fresh) 67-56-1 0.222 6.67 Dichloromethane 75-09-2 21.111 633.33 Aluminium Chloride 7446-70-0 0.778 23.33 Sulfuric Acid 7664-93-9 10.000 300.00 Sodium Cyanide 143-33-9 0.667 20.00 Di Methyl Carbonate 616-38-6 1.667 50.00 Total 37.56 1126.67

Product wise raw materials for remaining products will be covered in EIA report.

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 11 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal ANNEXURE- VI

MANUFACTURING PROCESS: 1) 5-Nitrofurfural diacetate Process: Acetic anhydride and Sulphuric acid is treated with Nitric acid gives 5-NLTA which on Hydrolysis gives 5-Nitrofurfural diacetate.

Chemical Reaction:

Material Balance & Flow Diagram:

2) 1-Amino hydantoin Process: Hydrazine Hydrate is treated with Urea in presence of Methanol gives 2-PSB which on cyclization with Methyl Chloroacetate gives PSAH.

PSAH further treated with HCl to give final product 1-Amino hydantoin.

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 12 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Chemical Reaction:

Material Balance & Flow Diagram:

3) Phosphoryl Choline chloride, Calcium salt. Process: Choline chloride is reacted with Phosphorous oxychloride to give Phosphroryl choline chloride, which subjected to hydrolysis and converted to Calcium salt to give the desired product Phosphoryl Choline chloride , Calcium salt. Chemical Reaction:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 13 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Material Balance & Flow Diagram:

4) Citicoline intermediate – 1 (CTS Tech) Process: Cytidine Monophospahte (CMP) dissolved in Methanol in presence of Dicyclohexy Carbodamide (DCC) and then condensed with Phosporyl Choline chloride at ambient temperature. After completion of reaction the reaction mass is filtered and final product is purified in Methanol. Chemical reaction:

NH O 2 NH O 2 P O NN O O N O P NN O NH + OH O DCC OH OH Methanol O O OH OH OH OH (5'-CMP-morpholidate)

CH 3 O Morpholine Cytidine 5'-monophosphate + - (5'-CMP) N Cl P O 3CH O CH 3 O Ca (CPCC) Methanol HCl IPA

NH 2 NH CH O O O 2 3 CH 3 O + N P P O + O NN N P P NN CH O O O 3 - 3CH O O O CH O Water - 3 ONa CH 3 O OH DIPA + Oxalic acid O O OH OH Formic acid OH OH Activated Carbon Citicoline Sodium Crude / Citicoline sodium Tech Sodium hydroxide Citicoline Acid Crude Purification Methanol + IPA Water Formic acid Sodium hydroxide Methanol + IPA

O NH 2 CH 3 O

+ O N P P NN CH O O O 3 - CH 3 O ONa O OH OH Citicoline Sodium - API

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 14 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Material balance & flow diagram:

5) 3-(1-CYANOETHYL) BENZOIC ACID Process:

Benzoic acid is treated with formaldehyde in presence of aluminium chloride in dichloromethane followed by esterification reaction with methanol in sulphuric acid gives methyl 3-(chloromethyl) benzoate which on further treated with sodium cyanide in methanol gives methyl 3- (cyanomethyl)benzoate. Methyl 3-(cyanomethyl) benzoate further methylated with dimethyl carbonate in water gives 3-(1- cyanoethyl) benzoic acid.

Chemical reaction:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 15 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Material balance & flow diagram:

6) 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodimide Hydrochloride (EDC. HCl) Process: Ethyl isothiocynate treated with N,N-Dimethyl-1,3-propanediamine in presence of sodium hypochlorite, potassium hydroxide in calcium carbonate treatment in chloroform as solvent, after completion of reaction, reaction mass is quenched with water and isolated product 1-ethyl-3-(3- dimethylaminopropyl) carbodimide. Further,1-ethyl-3-(3-dimethylaminopropyl) carbodimide further treated with anhydrous hydrochloric acid in acetonitrile solvent to give 1-ethyl-3-(3-dimethylaminopropyl) carbodimide hydrochloride. Chemical Reaction: CH 3 NaOCl, Chloroform CH3 NH N CH N 3CH N S + 2 3 NN

CH3 CH Isothiocyanatoethane 3 N,N-dimethylpropane-1,3-diamine N-[3-(dimethylamino)propyl]- N'-ethylcarbodiimide Molecular Formula = C 3H5NS Molecular Formula = C 5H14 N2 Formula Weight = 87.1435 Formula Weight = 102.17806 Molecular Formula = C 8H17 N3 Formula Weight = 155.24068

HCl CH3 CH N NN 3 HCl

CH3 N-[3-(dimethylamino)propyl]- N'-ethylcarbodiimide.hydrochloride (EDC.HCl)

Molecular Formula = C 8H17 N3 Formula Weight = 155.24068

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 16 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Material balance & flow diagram:

7) Quinuclidinone Process: Ethyl Piperidine 4-carboxylate has been treated with ethylchloro acetate in toluene solvent in presence of potassium carbonate as base. Reaction mass was refluxed for completion of reaction. Reaction mass was quenched with water. Organic layer was washed with water and toluene layer was subjected to next reaction Insitu. To above toluene layer charged potassium tert-butoxide and refluxed till completion of reactions. After this charge hydrochloric acid in to reaction mass and product was extracted in water. This acidic aqueous layer was refluxed for 24 hrs and finally product extracted in chloroform at basic pH. Distilled chloroform and IPA.HCl was added in to it. Filter precipitated product and dried under vacuum. Chemical Reaction:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 17 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Material balance & flow diagram:

8. 2-(4-AMINOPENTYL (ETHYL) AMINO) ETHANOL

Process: 5-Chloro-2-pentanone is treated with N-ethyl ethanol amine and organo-copper catalyst in xylene. Reaction mass was refluxed till completion of reaction followed by distillation of xylene. Obtained intermediate residue was treated with methanolic ammonia and raney nickel in methanol. After separation of catalyst, distilled methanol to get 2-(4-aminopentyl (ethyl) amino) ethanol. Chemical Reaction: O O Xylene CH OH Cl OH 3 CH 3 + 3CH NH Cu N

5-chloropentan-2-one 2-(ethylamino)ethanol Molecular Formula = C 5H9ClO Molecular Formula= C H NO CH 3 Formula Weight = 120.57 4 11 Formula Weight = 89.13 5-[ethyl(2-hydroxyethyl)amino]pentan-2-one

Molecular Formula = C 9H19 NO 2 2NH Formula Weight = 173.25 Raney Nickel

Methanol + NH 3 3CH OH N

CH 3 2-[(4-aminopentyl)(ethyl)amino]ethanol

Molecular Formula = C 9H22 N2O Formula Weight = 174.28

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 18 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Material balance & flow diagram:

9. 1-(p-methoxy benzyl)-1,2,3,4,5,6,7,8,Octahydro iso quinaline- S-octa base

Stage-I: 1-(p-methoxy benzyl)-1,2,3,4,5,6,7,8,Octahydro iso quinaline

Process: Cyclohexenylethylamine reacts with P-methoxyphenylacetic acid in Toluene gives N-(2- (Cyclohexen-1-yl)ethyl) -p-methoxyphenylacetamide .

Chemical Reaction:

Stage-II: 1-(p-methoxy benzyl)-1,2,3,4,5,6,7,8,Octahydro iso quinaline Mandelate

Process: N-(2-(Cyclohexen-1-yl)ethyl)-p-methoxyphenylacetamide reacts with Phosphorusoxychloride in Toluene gives 1-(P-methoxybenzyl)-3,4,5,6,7,8, hexahydroisoquinoline. Chemical Reaction:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 19 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

Stage-III: 1-(p-methoxy benzyl)-1,2,3,4,5,6,7,8,Octahydro iso quinaline- S-octa base

Process: 1-(P-methoxybenzyl)3,4,5,6,7,8, hexahydroisoquinoline reacts with Sodiumborohydride in Water gives 1-(P- methoxybenzyl)1,2,3,4,5,6,7,8, octahydroisoquinoline.,8, octahydro. Chemical Reaction:

Material Balance:

10. Dextrometharphin free base –Crude

Stage-I: (p-methoxybenzyl)-2-formyl-1,2,3,4,5,6,7,8, Octahydro iso quinaline

Process: D-1-(P-methoxybenzyl)1,2,3,4,5,6,7,8, octahydroisoquinolineMandalate reacts with Caustic lye in water gives D-1-(P-methoxybenzyl)1,2,3,4,5,6,7 isoquinoline (S-Octabase). Chemical Reaction:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 20 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Stage-II : 3--methoxy-N-formylmorphian

Process: Formulation of S-Octabase with Methyl formate in presence of Sodium methoxide and Toluene followed by neutralization with formic acid give Stage-II compound.

Chemical Reaction:

Stage-III: 3- methoxymorphian-Deformylation

Process:

Cyclization of stage-II compound in presence of Phosphoric acid give Stage-III.

Chemical Reaction:

Stage-IV

Process: High vacuum distillation of Stage-IV give pure compound i.e. Stage-V. Chemical Reaction:

Stage-V : Dextrometharphin free base -Crude

Process: N-methylation of Stage-IV with formaldehyde and formic acid in presence of Toluene followed by crystallization in Acetone gives Stage-V i.e. Dextromethorphan base. Chemical Reaction:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 21 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Material Balance:

11. Cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3- dioxolan-4-yl methyl methane sulfonate (CRUDE)

Stage- I

Process: 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-3H-1,2,4-triazol-3-one is reacted with 2-bromo butane to give 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-(1- methylpropyl)-3H-1,2,4-triazol-3-one. O O NH N

H3CO N N N H3CO N N N N N Stage – II: 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H- 1,2,4-triazol-3-one is reacted with hydro bromic acid to give 2,4-Dihydro-4-[4-[4-(4- hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one. O O N N H CO N 3 N N OH N N N N N

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 22 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Stage–IV: cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3-dioxolan-4-yl methanol is reacted with methane sulfonyl chloride to give cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl- methyl)-1,3-dioxolan-4-yl methyl methane sulfonate (Crude).

N N N N Cl N Cl N O O CH OSO CH Cl CH2OH Cl 2 2 3 O O H H Material Balance:

12. Cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3- dioxolan-4-yl methyl methane sulfonate (PURE)

Stage- I: 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-3H-1,2,4-triazol-3-one is reacted with 2-bromo butane to give 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2- (1-methylpropyl)-3H-1,2,4-triazol-3-one. O O NH N

H3CO N N N H3CO N N N N N

Stage – II: 2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H- 1,2,4-triazol-3-one is reacted with hydro bromic acid to give 2,4-Dihydro-4-[4-[4-(4- hydroxyphenyl)-1-piperazinyl]phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazol-3-one.

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 23 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

O O N N H CO N 3 N N OH N N N N N

Stage – III: cis-(2-Bromo methyl)-2-(2,4-dichloro phenyl)-1,3-dioxolan-4-yl methyl benzoate is reacted with 1H-1,2,4-triazole and the resultant is hydrolised with sodium hydroxide to give cis-2- (2,4-dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3-dioxolan-4-yl methanol. N Cl Br N Cl O N Cl CH2COOC6H5 O O Cl CH2OH H O H Stage–IV: cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl-methyl)-1,3-dioxolan-4-yl methanol is reacted with methane sulfonyl chloride to give cis-2-(2,4-Dichloro phenyl)-2-(1H-1,2,4-triazol-1-yl- methyl)-1,3-dioxolan-4-yl methyl methane sulfonate.

N N N N Cl N Cl N O O CH OSO CH Cl CH2OH Cl 2 2 3 O O H H

Stage – V: 4-[4-[4-(4-Hydroxyphenyl)-1-piperazinyl]phenyl]-2,4-dihydro- 2-(1- methylpropyl)-3H-1,2,4-triazole-3-one is reacted with cis-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol- 1-yl-methyl)-1,3-dioxolan-4-yl methyl methane sulfonate and sodium hydroxide, in toluene and methanol to give Itraconazole (Pure).

N N CH O 3 Cl N N O OH NN N CH + 3 Cl CH2OSO2CH3 N O H

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 24 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Material Balance:

13. KeterolacTrimethamine INTERMEDIATES

Stage – I: Marpholine phenyl methanone Process: Morpholine reacted with Benzoyl chloride In presence of Toluene gives Marpholine phenyl methanone Chemical Reaction:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 25 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

Material Balance:

Stage-II : Phenyl (1h pyrrole-2-yl)methanone. Process: Marpholine phenyl methanone reacted with pocl3 and pyrrole after that quenching in Ice water isolated product gives Phenyl (1h pyrrole-2-yl)methanone. Chemical Reaction:

Material Balance:

Stage- III

Process: Magnesium oxide and dimethyl Malenate reacted with Ethyl Choloroformate and Sulfuric acid in presence of Toluene gives Triethyl methane tricarboxylate. Material Balance:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 26 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Stage- IV: Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate .

Process: Triethyl methane tricarboxylate and Phenyl (1h pyrrole-2-yl)methanone in presense of magnesium acetate and acetic anhydride in presence of ethyl acetate gives Phenyl (1h pyrrole-2- yl)methanone – tricarboxylate.

Chemical Reaction:

Material Balance:

Stage- V: Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate .

Process: Phenyl (1h pyrrole-2-yl) methanone – tricarboxylate reacted with potassium carbonate in presence of ethyl acetate by using TBAB catalyst Gives Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate crude.

Chemical Reaction:

Material Balance:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 27 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Stage–VI: Process: Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate -Ketrolactrimethamin -crude .

Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate reacted with Triethl amine in presence of Acetone Gives Phenyl (1h pyrrole-2-yl)methanone – tricarboxylate -Ketrolactrimethamin -crude .

Chemical Reaction:

Material Balance:

14. (-)-1-[(4-Chlorophenyl)phenylmethyl]-4-[(4-methylphenyl) sulfonyl] piperazine

Stage-1: Reaction of p-Chloro benzo phenone (PCBP) with Ammonium formate in toluene followed by workup gives racemic (±)-(4-Chlorophenyl) phenylmethyl amine (Stage-I Intermediate). Chemical Reaction:

Stage-II: Treatment of Stage-I intermediate with L(+)-Tartaric acid in methanol provides the required isomer as its tartaric acid salt, which on hydrolysis with aq. sodium hydroxide gives Levorotatory (-)- (4-Chlorophenyl) phenylmethyl amine (Stage-II intermediate) as an oily liquid.

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 28 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Chemical Reaction:

Stage-III: Treatment of N,N-Bis (2-chloroethyl)amine hydrochloride with p-Toluene Sulphonyl chloride in Methylene dichloride and followed by workup yields N,N-bis(2-Chloroethyl)-4-methyl benzene sulfonamide (Stage-III intermediate)

Chemical Reaction:

Stage-IV: Condensation of Levorotatory (-)-(4-Chlorophenyl) phenyl methyl amine (Stage-II intermediate) with N,N-bis(2-Chloroethyl)-4-methyl benzene sulfonamide (Stage-III intermediate) in presence of Disopropyl ethylamine (DIEPA) and followed by further workup yields (-)-1-[(4-

Chlorophenyl)phenylmethyl]-4-[(4-methylphenyl)sulfonyl] piperazine (Stage-IV intermediate).

Chemical Reaction:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 29 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

Material Balance:

15. (-) P-Chloro benzhydryl piperazine

Stage-1 : Reaction of p-Chloro benzo phenone (PCBP) with Ammonium formate in toluene followed by workup gives racemic (±)-(4-Chlorophenyl) phenylmethyl amine (Stage-I Intermediate). Chemical Reaction:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 30 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Stage-II: Treatment of Stage-I intermediate with L(+)-Tartaric acid in methanol provides the required isomer as its tartaric acid salt, which on hydrolysis with aq. sodium hydroxide gives Levorotatory (-)- (4-Chlorophenyl) phenylmethyl amine (Stage-II intermediate) as an oily liquid.

Chemical Reaction:

Stage-III: Treatment of N,N-Bis (2-chloroethyl) amine hydrochloride with p-Toluene Sulphonyl chloride in Methylene dichloride and followed by workup yields N,N-bis(2-Chloroethyl)-4-methyl benzene sulfonamide (Stage-III intermediate).

Chemical Reaction:

Stage-V: Treatment of Stage-IV intermediate with HBr in acetic acid in presence of p Hydroxy benzoic acid (catalyst) followed by workup gives (-) p-Chloro benzhydryl piperazine (Stage-V).

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 31 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Chemical Reaction:

Material Balance:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 32 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

16. 2,3 pyrridine Benzyle carboxylate Hydrate Chloro compound

Process:

Stage-I: 2,3 pyrridineBenzyle carboxylate

2,3 pyrridine dicarboxylic acid reacted acetic anhydride and benzyl amine In presence of Methanol and toluene gives 2,3 pyrridineBenzyle carboxylate.

Stage-II: 2,3 pyrridineBenzyle carboxylate hydrate

2,3 pyrridine Benzyl carbaxylate reacted with Palladium carbon catalyst in presence of ethyacetate gives 2,3 pyrridineBenzyle carboxylate hydrate.

Stage-III : 2,3 pyrridineBenzyle carboxylate Hydrate Tartrate salt

2,3 pyrridineBenzyle carboxylate hydrate reacted with tartaric acid inpresence of Water gives 2,3 pyrridineBenzyle carboxylate tartrate salt.

Stage- IV: 2,3 pyrridineBenzyle carboxylate Hydrate Chloro compound

2,3 pyrridineBenzyle carboxylate tartrate salt reacted with Alluminium chloride inpresence of Water and toluene gives 2,3 pyrridineBenzyle carboxylate chlorcompound. Stage-V: 2,3 pyrridineBenzyle carboxylate Hydrate Chloro compound

2,3 pyrridineBenzyle carboxylate clorocompound reacted with Hydrogenation reduction inpresence of Water and Methanol gives Nonane compound.

Chemical Reaction:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 33 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

Material Balance:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 34 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

17. 3,4-dimethoxy-2-chloro methyl pyridine

Stage-I: Maltol is reacts with Dimethyl sulphate in presence of acetone to get 3-methoxy 2-methyl-4- pyron.

Stage-II: 3-methoxy n-methyl-4-pyron reacts with liquor ammonia solution and ammonia acetate is used as a catalyst crystallized by the acetone 3-methoxy 2-methyl-4-pyridone.

Stage-III: 3-methoxy 2-methyl-4-pyridone reacts with phosphorous oxychloride in presence of MDC to get 4-chloro 3-methoxy 2-methyl-4-pyridone.

Stage-IV: 4-chloro 3-methoxy 2-methyl-4-pyridone reacts with hydrogen peroxide in presence of acetic acid sodium tungastate is under as a catalyst 4-chloro 3-methoxy 2-methyl-4-pyridone-n-oxide.

Stage-V: 4-chloro 3-methoxy 2-methyl-4-pyridone-n-oxide reacts with methanol in presence of sodium hydroxide to get 3,4-diethoxy-2-methyl-4-pyridone-n-oxide.

Stage-VI: 3,4-diethoxy-2-methyl-4-pyridone-n-oxide reacts with acetic anhydride and further reacts with sodium hydroxide in presne of water to get 3,4-dimethoxy-2-hydroxy methyl pyridine.

Stage-VII: 3,4-dimethoxy-2-hydroxy methyl pyridine reacts with thionyl chloride in presence of MDC 3,4-dimethoxy-2-chloro methyl pyridine- pantoprazole chloro.

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 35 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Chemical Reaction:

Material Balance:

18. Pentaprozole sulphide

Stage-I: Maltol is reacts with Dimethyl sulphate in presence of acetone to get 3-methoxy 2-methyl-4- pyron.

Stage-II: 3-methoxy n-methyl-4-pyron reacts with liquor ammonia solution and ammonia acetate is used as a catalyst crystallized by the acetone 3-methoxy 2-methyl-4-pyridone.

Stage-III: 3-methoxy 2-methyl-4-pyridone reacts with phosphorous oxychloride in presence of MDC to get 4-chloro 3-methoxy 2-methyl-4-pyridone.

Stage-IV: 4-chloro 3-methoxy 2-methyl-4-pyridone reacts with hydrogen peroxide in presence of acetic acid sodium tunga state is under as a catalyst 4-chloro 3-methoxy 2-methyl-4-pyridone-n-oxide.

Stage-V: 4-chloro 3-methoxy 2-methyl-4-pyridone-n-oxide reacts with methanol in presence of sodium hydroxide to get 3,4-diethoxy-2-methyl-4-pyridone-n-oxide.

Stage-VI: 3,4-diethoxy-2-methyl-4-pyridone-n-oxide reacts with acetic anhydride and further reacts with sodium hydroxide in presne of water to get 3,4-dimethoxy-2-hydroxy methyl pyridine.

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 36 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Stage-VII: 3,4-dimethoxy-2-hydroxy methyl pyridine reacts with thionyl chloride in presence of MDC 3,4-dimethoxy-2-chloro methyl pyridine- pantoprazole chloro.

Stage-VIII: 5-(Difluoro methoxy)-2-mercapto benzimidazole and 2-chloromethyl-3,4-dimethoxy- pyridine hydrochloride are condensed in the presence of sodium hydroxide and in methanol to give 5-(Difluoro methoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)-2-methyl] thiol]-1H-benzimidazole to get pentaprozole sulphide.

Chemical Reaction:

Material Balance:

19. Pregabalin (Racemic)

Stage-I: Isovelaraldehyde is reacts with Ethyl cyan Acetate in presence of Toluene to get 2-Carboxy- 5-methyl hex-2- exotic acid ethyl ester.

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 37 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Stage-II: 2-Carboxy-5-methyl hex-2-exotic acid ethyl ester reacts with R-Phenyl |Ethyl amine in presence of Chloroform to get 2-Carboxyethyl-3-cyano-5-methyl hexanoic acid ethyl ester.

Stage-III: 2-Carboxyethyl-3-cyano-5-methyl hexanoic acid ethyl ester reacts with Bromine in presence of MDC to get Pregabalin (Racemic).

Chemical Reaction:

Stage-I : Preparation of 2-Carboxy-5-methyl hex-2-exotic acid ethyl ester

Stage-II : Preparation of 2-Carboxyethyl-3-cyano-5-methyl hexanoic acid ethyl ester

Stage-III : Preparation of Pregabalin (Racemic)

Stage-IV : Preparation of Pregabalin

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 38 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Material Balance:

20. 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride

Process:

Stage – I: 2-Amino diphenyl sulphide is reacted with Phenylchloroformate in presence of Toluene gives Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1).

Stage – II: Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1) is reactes with Poly phosphouric acid in presence of Acetone to give Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I).

Stage – III: Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)is reacted with Pocl3 in presence of Piperazine to give 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride.

Chemical Reaction: Preparation of Phenyl -2- (-phenylthio)phrnyl carbamate (QUE-1) NHCOOPh NH2 O Na CO 2 3 S S + C6H5-O-C-Cl

2-Aminodiphenyl sulphide Phenyl-2-(phenylthio)phenyl carbamate

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 39 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Preparation of Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I) H O NHCOOPh N Polyphosphoric acid S S

Phenyl-2-(phenylthio)phenyl carbamate Dibenzo [b,f][1,4]thiazepine-11(10-H)one

Preparation of 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride (QUE-III HCl):

Material Balance: Stage-I: Preparation of Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1):

Stage-II: Preparation of Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)

Stage-III: Preparation of 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride (QUE-III)

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 40 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal 21. 11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1-piperazinyl] dibenzo (b, f) (1, 4) thiazepine hemifumarate

Process:

Stage – I: 2-Amino diphenyl sulphide is reacted with Phenylchloroformate in presence of Toluene gives Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1).

Stage – II: Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1) is reactes with Poly phosphouric acid in presence of Acetone to give Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I).

Stage – III: Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)is reacted with Pocl3 in presence of Piperazine to give 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride.

Stage – IV: 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride is reacts with N-methyl pyrrolidinone in presence of 2-chloro ethoxy ethanol 11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1- piperazinyl] dibenzo (b, f) (1, 4) thiazepine hemifumarate (QUE-IV).

Chemical Reaction:

Preparation of Phenyl -2- (-phenylthio)phrnyl carbamate (QUE-1) NHCOOPh NH2 O Na CO 2 3 S S + C6H5-O-C-Cl

2-Aminodiphenyl sulphide Phenyl-2-(phenylthio)phenyl carbamate Preparation of Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I) H O NHCOOPh N Polyphosphoric acid S S

Phenyl-2-(phenylthio)phenyl carbamate Dibenzo [b,f][1,4]thiazepine-11(10-H)one

Preparation of 11-Piperazinyl-dibenzo(b,f) (1,4)-thiazepine hydrochloride (QUE-III HCl):

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 41 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Preparation of 11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1-piperazinyl] dibenzo (b, f) (1, 4) thiazepine hemifumarate (QUE-IV).:

Material Balance: Stage-I: Preparation of Phenyl-2-(phenyl thio) phenyl carbamate (QUE-1):

Stage-II: Preparation of Dibenzo (b, f) (1,4) thiazepine-11 (10H)-one (QUE-1I)

Stage-III: Preparation of 11-Piperazinyl-dibenzo (b,f) (1,4)-thiazepine hydrochloride (QUE-III)

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 42 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Stage- IV: Preparation of 11-[4-[2-(2-Hydroxy ethoxy) ethyl]-1-piperazinyl] dibenzo (b, f) (1, 4) thiazepine hemifumarate (QUE-IV)

22. 2-[(4-(3-methoxypropoxy)-3-methyl- 2-pyridinyl) methyl]thio]-1H-benzimidazole

Stage – I: 2,3-Dimethyl-4-nitropyridine-N-oxide is reacted with dry HCl and isopropyl alcohol to give 4-chloro-2,3-dimethylpyridine-N-oxide hydrochloride.

Chemical Reaction:

Stage – II: 4-Chloro-2,3-dimethylpyridine-N-oxide hydrochloride is condensed with 3-methoxy-1- propanol and rearranged with acetic anhydride and is hydrolyzed with sodium hydroxide and is neutralized with dry HCl to give 2-hydroxymethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride.

Chemical Reaction:

Stage – III: 2-Hydroxymethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride is reacted with thionyl chloride to give 2-chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride.

Chemical Reaction:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 43 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Stage – IV: 2-Chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride is condensed with 2-mercapto-1H-benzimidazole to give 2-[[(4-(3-methoxypropoxy)-3-methyl- 2-pyridinyl)methyl] thio]-1H-benzimidazole.

Chemical Reaction:

Material Balance:

23. 2-[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole

Process:

Stage – I: 2,3-Dimethyl-4-nitropyridine-N-oxide is reacted with dry HCl and isopropyl alcohol to give 4-chloro-2,3-dimethylpyridine-N-oxide hydrochloride.

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 44 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Chemical Reaction:

Chemical Reaction:

Stage – III: 2-Hydroxymethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride is reacted with thionyl chloride to give 2-chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride.

Chemical Reaction:

Stage – IV: 2-Chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride is condensed with 2-mercapto-1H-benzimidazole to give 2-[[(4-(3-methoxypropoxy)-3-methyl- 2-pyridinyl)methyl] thio]-1H-benzimidazole.

Chemical Reaction:

Stage–V: 2-[[(4-(3-Methoxypropoxy)-3-methyl-2-pyridinyl)-2-methyl]thio]-1H-benzimidazole oxidized to give 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole

Chemical Reaction:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 45 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal Material Balance:

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 46 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

ANNEXURE- VII

DETAILS OF WATER CONSUMPTION

Category Water Consumption (KLD) Remarks (A) Domestic 20.0 20.0 KLD Fresh

(B) Gardening 10.0 10.0 KLD Fresh

(C)Industrial i. Process 85.0 85.0 KLD Recycle ii. Boiler 30.0 30.0 KLD Fresh iii. Cooling 40.0 17.0 KLD Fresh + 23.0 KLD Recycle iv. Washing 27.0 27.0 KLD Recycle v. Others 10.0 10.0 KLD Recycle - For Scrubber

Industrial Total 192.0 47.0 KLD Fresh + 145.0 KLD Recycle Total (A+ B +C) 222.0 77.0 KLD Fresh + 145.0 KLD Recycle

DETAILS OF WASTE WATER GENERATION

Category Wastewater generation(KLD) Remarks (A) Domestic 15.0 To soak pit

(B) Industrial i. Process 120.0 Send to ETP for treatment ii. Boiler 3.0 Send to ETP for treatment iii. Cooling 2.0 Send to ETP for treatment iv. Washing 27.0 Send to ETP for treatment v. Others 10.0 Send to ETP for treatment

Effluent will be treated in ETP and RO Total Industrial 162.0 & recycle back in the unit. Unit will waste water achieve zero liquid discharge. Total (A + B) 177.0 ------

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 47 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal

DETAILS OF WATER BALANCE DIAGRAM

Total Water Consumption 222.0 KLD

(77.0 KLD Fresh + 145.0 KLD Recycle)

Water recycles in Process+ Washing + Cooling Total Industrial – 192.0 47.0 KLD (F) + 145.0 KLD (R) Domestic Gardening 20 KLD (F) 10 KLD (F)

Process Boiler Cooling Washing Scrubber Sewage Effluent 85.0 KLD (R) 30.0 KLD (F) Total- 40.0 KLD 27.0 KLD (R) 10.0 KLD (R) 17.0 (F) + 23.0 (R) 15 KLD

To Soak Pit

Effluent Boiler B. D. Cooling tower 27.0 KLD 10.0 KLD 120.0 KLD 3.0 KLD 2.0 KLD

Solvent stripper Total Effluent generation Send for co-processing 162.0 KLD 7.0 KLD

155.0 KLD

Recycle To ETP for Treatment water 155.0 KLD

RO Permeate RO Reject To RO Plant 105 KLD 50 KLD

Recycle Send to MEE water 50.0 KLD

Salt Condensate

40.0 KLD 10 .0 KLD

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 48 M/s. Ishanga Life Science Pvt. Ltd. Madhvas, Tal. Kalol, Dist.: Panchmahal ANNEXURE-VIII

DETAILS OF ELECTRICITY AND FUEL CONSUMPTIONS

Sr. Particulars Proposed Quantity Remark Source No. Bio-coal 3 ton boiler considered at 1. (Coal-in case of non 7.0 MT/day Local availability of bio-coal during 40% load monsoon) 2. Electricity 750 KVA On peak load MGVCL

3. Saw dust 4.5 MT/day Alternate fuel for Boiler Local

Use for DG set in 4. Diesel 80 Lit/Hr Local emergency case

ANNEXURE- IX

DETAILS OF FLUE GAS EMISSIONS

Stack Fuel Stack Permissible Stack Attached to APCM Parameter No. Consumption Height (m) Limit Bio-coal/Coal Multi cyclone 1. Boiler (3 TPH) 11.0 separator & Particulate 150 7.0 MT/Day bag filter Matter mg/Nm 3 D. G. Set (Capacity-600 SO 100 ppm Diesel Adequate 2 2. KVA) 9.0 80 Lit/hr stack height Emergency case NO x 50 ppm only

ANNEXURE- X

DETAILS OF PROCESS EMISSION

Stack Stack Permissible Stack Attached to APCM Parameter No. Height (m) Limit 2 Stage Water 1. Reactor- I 11.0 Ammonia 175 mg/ Nm3 scrubber 2. Reactor - II 11.0 Alkali scrubber Chlorine 9.0 mg/ Nm3 HCl 20.0 mg/ Nm3 3. Reactor – III 11.0 Alkali scrubber NO x 50 ppm

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar. 49 M/s. Mahansaria Tyre Pvt. Ltd. , Panoli

ANNEXURE- XI

DETAILS OF HAZARDOUS WASTE

Sr. Source of Quantity Type of Wastes Category Mode of disposal No. Generation MT/Annum Collection, Storage within premises, Effluent 1 ETP Waste 34.3 7115.0 Transportation and Disposal at TSDF of Treatment NECL, Nandesari Maintenance and used lubricant oil Collection and Storage within premises 2 Used Oil 5.1 generated from 0.400 & Disposal by selling to registered re- Maintenance processor. Activities Collection, Storage and Decontamination Discarded Containers/ 3 33.3 Packing Materials 100.0 within premises & Disposal by selling to Bags/Liners authorized re-cycler. Collection, Storage, Transportation and 4 Process Residue 28.1 Process 8415.0 Selling to authorize recycler/NECL.

Process 25.0 Collection, Storage, transportation and 5 Spent Carbon 28.3 send for co-processing to NECL. ETP 24.0 Collection, Storage within premises, 6 Spent catalyst 28.2 Process 1650.0 Transportation and Disposal at TSDF of NECL/ sent to recycler for activation. Collection, Storage and send to ETP for 7. Scrubber solution --- Process 3000 treatment. Collection, storage and send for solvent Effluent 8. Stripper solvent 28.6 2520 recovery/ co-processing/ solvent Treatment recovery Co llection, Storage within premises, 9. MEE Salt 37.3 MEE 3600.0 Transportation and Disposal at TSDF of NECL. Collection, Storage, transport ation and 10 Used membranes --- RO Plant 2.0 send for land filling to NECL.

M/s. Jyoti Om Chemical Research Centre Pvt. Ltd., Ankleshwar 50