Processes and intermediates for producing azaindoles

• US 9,090,614 B2
• Filed: 12/15/2014
• Issued: 07/28/2015
• Est. Priority Date: 07/05/2011
• Status: Expired due to Fees

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Tanoury, Gerald J., Jung, Young Chun, Magdziak, Derek, Looker, Adam, Kline, Billie J., Jurck, Vclav, Dominguez Olmo, Beatriz
• Primary Examiner(s): VAJDA, KRISTIN ANN
• Application Number:
  US14/570,044
• Publication Number:
  US 20150099884A1
• Time in Patent Office: 225 Days
• Field of Search: 544/328
• US Class Current: 1/1
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 239/42 One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: C07F 5/04 Esters of boric acids

Abstract

The present invention relates to processes and intermediates for the preparation of compounds useful as inhibitors of Janus kinases (JAK).

Claims

1. A solid form of (R)-2-(2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-2-methylbutanoic acid (4a) designated as Form E.

2. The solid Form E of claim 1, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 7.1±

0.2, 8.2±

0.2, 23.9±

0.2, and 24.8±

0.2 in an X-ray powder diffraction pattern.

3. A solid form of (R)-2-(2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-2-methylbutanoic acid (4a) designated as Form B.

4. The solid Form B of claim 3, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 9.2±

0.2, 18.1±

0.2, 19.1±

0.2, and 32.0±

0.2 in an X-ray powder diffraction pattern.

5. The solid Form B of claim 4, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 21.4±

0.2, 30.1±

0.2, 29.9±

0.2, and 26.1±

0.2 in an X-ray powder diffraction pattern.

9. The solid Form B of claim 3, further characterized by a dehydration temperature of about 73°

C.

10. The solid Form B of claim 3, further characterized by an onset temperature of about 40°

C.

11. The solid Form B of claim 3, further characterized by a dehydration heat of about 725 J/g.

12. The solid Form B of claim 3, further characterized by a dehydration temperature of about 137°

C.

13. The solid Form B of claim 3, further characterized by an onset temperature of about 166°

C.

14. The solid Form B of claim 3, further characterized by a dehydration heat of about 42 J/g.

6. A solid form of (R)-2-(2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)-2-methyl-N-(2,2,2-trifluoroethyl)butanamide (Ia) designated as Form A.

7. The solid Form A of claim 6, characterized by one or more peaks corresponding to 2-theta values measured in degrees of 23.7±

0.2, 11.3±

0.2, 19.3±

0.2, and 15.4±

0.2 in an X-ray powder diffraction pattern.

8. The solid Form A of claim 7, further characterized by one or more peaks corresponding to 2-theta values measured in degrees of 28.9±

0.2 and 21.5±

0.2 in an X-ray powder diffraction pattern.

15. The solid Form A of claim 6, further characterized by a melting point of about 262°

C.

16. The solid Form A of claim 6, further characterized by an onset temperature of about 260.8°

C.

17. The solid Form A of claim 6, further characterized by a melting heat of about 140.5 J/g.