Claims for Patent: 10,010,530

Summary for Patent: 10,010,530

Title:	Carboxamide derivative and its diastereomers in stable crystalline form
Abstract:	The present disclosure relates to solid crystalline forms of N--((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-5-(1-- hydroxyethyl)-1H-pyrazole-3-carboxamide (I) and the diastereomers thereof, and to methods for preparing such crystalline forms. Compound (I) and the diastereomers thereof are potent androgen receptor (AR) modulators useful as a medicament. ##STR00001##
Inventor(s):	Tormakangas; Olli (Turku, FI), Heikkinen; Terhi (Lieto, FI)
Assignee:	Orlon Corporation (Espoo, FI)
Application Number:	15/547,193
Patent Claims:	1. Crystalline form I of N--((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl) propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (I) having an X-ray powder diffraction pattern comprising characteristic peaks at about 8.5, 10.4, 16.6, 16.9, and 24.3 degrees 2-theta. 2. Crystalline form I' of N--((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-((S)- -1-hydroxyethyl)-1H-pyrazole-3-carboxamide (Ia) having an X-ray powder diffraction pattern comprising characteristic peaks at about 9.3, 15.7, 17.0, 24.1 and 25.1 degrees 2-theta. 3. Crystalline form I'' of N--((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-((R)- -1-hydroxyethyl)-1H-pyrazole-3-carboxamide (Ib) having an X-ray powder diffraction pattern comprising characteristic peaks at about 9.2, 10.9, 15.1, 15.8 and 22.1 degrees 2-theta. 4. A process for preparing crystalline form I, I' or I'' of N--((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl) propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (I), N--((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-((S)- -1-hydroxyethyl)-1H-pyrazole-3-carboxamide (Ia) or N--((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-((R)- -1-hydroxyethyl)-1H-pyrazole-3-carboxamide (Ib), respectively, comprising a) mixing N--((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl) propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (I), N--((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-((S)- -1-hydroxyethyl)-1H-pyrazole-3-carboxamide (Ia) or N--((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-((R)- -1-hydroxyethyl)-1H-pyrazole-3-carboxamide (Ib) with a mixture of acetonitrile and water; b) heating the mixture from step a) to form a solution; c) cooling the solution from step b) to about 0-50.degree. C.; and d) isolating the crystalline form. 5. The process according to claim 4, wherein the acetonitrile:water mixture has a volume ratio from about 85:15 to about 99:1. 6. The process according to claim 5, wherein the acetonitrile:water mixture has a volume ratio from about 90:10 to about 98:2. 7. The process according to claim 6, wherein the acetonitrile:water mixture has a volume ratio of about 95:5. 8. The process according to claim 4, wherein the cooling step c) occurs over about 5 to about 24 hours. 9. The process according to claim 8, wherein the cooling step c) occurs over about 6 to about 12 hours. 10. The process according to claim 4, wherein the isolated crystalline form is dried under vacuum at about 40.degree. C. to about 60.degree. C. 11. The crystalline form I of N--((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl) propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide (I) of claim 1, further having an X-ray powder diffraction pattern comprising characteristic peaks at about 9.7, 15.9, 19.2, 21.8 and 25.5 degrees 2-theta. 12. The crystalline form I' of N--((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-((S)- -1-hydroxyethyl)-1H-pyrazole-3-carboxamide (Ia) of claim 2, further having an X-ray powder diffraction pattern comprising characteristic peaks at about 11.4, 14.9, 17.7, 20.5 and 27.2 degrees 2-theta. 13. The crystalline form I'' of N--((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-((R)- -1-hydroxyethyl)-1H-pyrazole-3-carboxamide (Ib) of claim 3, further having an X-ray powder diffraction pattern comprising characteristic peaks at about 7.9, 16.9, 18.4, 20.2 and 21.8 degrees 2-theta.