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WO 2017/048702 Al (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date W O 2017/048702 A l 2 3 March 2017 (23.03.2017) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07D 487/04 (2006.01) A61P 35/00 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/519 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) International Application Number: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US20 16/05 1490 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 13 September 2016 (13.09.201 6) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (25) Filing Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (26) Publication Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 62/218,493 14 September 2015 (14.09.2015) US (84) Designated States (unless otherwise indicated, for every 62/218,486 14 September 2015 (14.09.2015) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (71) Applicant: INFINITY PHARMACEUTICALS, INC. TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, [US/US]; 780 Memorial Drive, Cambirdge, MA 021 39 TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (US). DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, (72) Inventors: CRENIER, Louis; 140 Sargent Street, New SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, ton, MA 02458 (US). LESCARBEAU, Andre; 99 Porter GW, KM, ML, MR, NE, SN, TD, TG). Street, Somerville, MA 02143 (US). SHARMA, Praveen; 16 Christine Road, Arlington, MA 02474 (US). GENOV, Published: Daniel G.; 160 Commonwealth Avenue, Apt 706, Boston, — with international search report (Art. 21(3)) MA 021 16 (US). — before the expiration of the time limit for amending the (74) Agents: BRUNER, Michael J . et al; Jones Day, 250 Ve- claims and to be republished in the event of receipt of sey Street, New York, NY 10281-1047 (US). amendments (Rule 48.2(h)) (54) Title: SOLID FORMS OF ISOQUINOLINONE DERIVATIVES, PROCESS OF MAKING, COMPOSITIONS COMPRIS ING, AND METHODS OF USING THE SAME 4000 3000 2000 o 1000 0 0 o 20 30 FIG. 1 2-Theta-Scale (57) Abstract: Solid forms of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphic forms, cocrystals, and amorphous forms thereof, and pharmaceutical compositions thereof. SOLID FORMS OF ISOQUINOLINONE DERIVATIVES, PROCESS OF MAKING, COMPOSITIONS COMPRISING, AND METHODS OF USING THE SAME [0001] This application claims priority to U.S. Provisional Application Nos. 62/2 18,486, filed September 14, 20 15, and 62/2 18,493, filed September 14, 2015, the entireties of which are incorporated herein by reference. 1 BACKGROUND [0002] The activity of cells can be regulated by external signals that stimulate or inhibit intracellular events. The process by which stimulatory or inhibitory signals are transmitted into and within a cell to elicit an intracellular response is referred to as signal transduction. Over the past decades, cascades of signal transduction events have been elucidated and found to play a central role in a variety of biological responses. Defects in various components of signal transduction pathways have been found to account for a vast number of diseases, including numerous forms of cancer, inflammatory disorders, metabolic disorders, vascular and neuronal diseases (Gaestel et al. CurrentMedicinal Chemistry (2007) 14:22 14-2234). [0003] Kinases represent a class of important signaling molecules. Kinases can generally be classified into protein kinases and lipid kinases, and certain kinases exhibit dual specificities. Protein kinases are enzymes that phosphoiylate other proteins and/or themselves (i. e., autophosphorylation). Protein kinases can be generally classified into three major groups based upon their substrate utilization: tyrosine kinases which predominantly phosphoiylate substrates on tyrosine residues (e.g., ert>2, PDGF receptor, EGF receptor, VEGF receptor, src, abl), serine/threonine kinases which predominantly phosphoiylate substrates on serine and/or threonine residues (e.g., mTorCl, mTorC2, ATM, ATR, DNA-PK, Akt), and dual-specificity kinases which phosphoiylate substrates on tyrosine, serine and/or threonine residues. [0004] Lipid kinases are enzymes that catalyze the phosphorylation of lipids. These enzymes, and the resulting phosphorylated lipids and lipid-derived biologically active organic molecules play a role in many different physiological processes, including cell proliferation, migration, adhesion, and differentiation. Certain lipid kinases are membrane associated and they catalyze the phosphorylation of lipids contained in or associated with cell membranes. Examples of such enzymes include phosphoinositide(s) kinases (e.g., PI3-kinases, PI4- Kinases), diacylglycerol kinases, and sphingosine kinases. [0005] Phosphoinositide 3-kinases (PI3Ks) constitute a unique and conserved family of intracellular lipid kinases that phosphorylate the 3' -OH group on phosphatidylinositols or phosphoinositides. The PI3K family comprises 15 kinases with distinct substrate specificities, expression patterns, and modes of regulation. The class I PI3Ks (pi 10a, p i 10β, p i 105, and p i 10γ) are typically activated by tyrosine kinases or G-protein coupled receptors to generate a lipid product termed PIP 3, which engages downstream effectors such as those in the Akt/PDKl pathway, mTOR, the Tec family kinases, and the Rho family GTPases. The class II and III PI3Ks play a key role in intracellular trafficking through the synthesis of PI(3)P and PI(3,4)P2. [0006] The PI3K signaling pathway is one of the most highly mutated systems in human cancers. PI3K signaling is also a key factor in many other diseases in humans. PI3K signaling is involved in many disease states including allergic contact dermatitis, rheumatoid arthritis, osteoarthritis, inflammatory bowel diseases, chronic obstructive pulmonary disorder, psoriasis, multiple sclerosis, asthma, disorders related to diabetic complications, and inflammatory complications of the cardiovascular system such as acute coronary syndrome. [0007] Many inhibitors of PI3Ks have been generated. While such compounds are often initially evaluated for their activity when dissolved in solution, solid state characteristics such as polymorphism play an important role. Polymorphic forms of a drug substance, such as an inhibitor of PI3K, can have different chemical and physical properties, including crystallinity, melting point, chemical reactivity, solubility, dissolution rate, optical and mechanical properties, vapor pressure, and density. These properties can have a direct effect on the ability to process or manufacture a drug substance and the drug product. Moreover, polymorphism is often a factor under regulatory review of the "sameness" of drug products from various manufacturers. For example, polymorphism has been evaluated in compounds such as warfarin sodium, famotidine, and ranitidine. Polymorphism can affect the quality, safety, and/or efficacy of a drug product, such as a kinase inhibitor. Thus, research directed towards polymorphs of PI3K inhibitors and processes for preparing polymorphs of PI3K inhibitors represents a significantly useful field of investigation in the development of active pharmaceutical ingredients (APIs). [0008] In addition, PI3K inhibitors have been used to treat various diseases and disorders in humans (e.g., in clinical trials). For the production of a drug substance intended for use in humans, current Good Manufacturing Practices (GMP) are applicable. Procedures need to be in place that can control the levels of impurities and ensure that API products are produced, which consistently meet their predetermined specifications. Thus, a significant need exists for a process to prepare PI3K inhibitors suitable for human use, particularly on a commercial scale, that is, inter alia, safe, scalable, efficient, economically viable, and/or having other desirable properties. Among other entities, disclosed herein are polymorphic forms of PI3K inhibitors which address these needs and provide exemplary advantages. 2 . SUMMARY [0009] Provided herein are solid forms comprising a compound of formula (I) (also referred as Compound 1 herein): or a salt, or solvate (e.g. , hydrate), or solvate of a salt thereof, or a mixture thereof. Also provided herein are methods of synthesizing the solid forms. [0010] The solid forms provided herein include, but are not limited to, hydrates, anhydrates, solvates of Compound 1 and salts and cocrystals thereof. The solid forms provided herein are useful as active pharmaceutical ingredients for the preparation of formulations for use in animals or humans. Thus, embodiments herein encompass the use of these solid forms as a final drug product. Certain embodiments provide solid forms useful in making final dosage
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