ISOTOPICALLY ENRICHED AZAINDOLES

• US 20160168147A1
• Filed: 02/22/2016
• Published: 06/16/2016
• Est. Priority Date: 08/22/2013
• Status: Abandoned Application

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Brummel, Christopher Lee, Dorsch, Warren, Maltais, Francois, Deininger, David D., Ledford, Brian
• Application Number:
  US15/049,812
• Publication Number:
  US 20160168147A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: C07B 59/002 Heterocyclic compounds
• CPC Class Codes: C07D 239/42 One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 239/95 with hetero atoms directly attached in positions 2 and 4
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds

Abstract

The present invention relates to deuterated compounds that are useful for inhibiting Janus kinases and processes and intermediates useful for preparing such compounds.

Claims

1. A compound having the structure:

2. A compound of Formula II-a:

3. The compound according to claim 2, wherein R⁵ is —

PG¹, and —

PG¹ is —

SO₂-phenyl or Boc, wherein the phenyl is optionally substituted with alkyl.

4. The compound according to claim 3, wherein the phenyl is unsubstituted.

5. The compound according to claim 2, wherein R⁶ is halo or —

B(OR⁷)₂.

6. The compound according to claim 5, wherein R⁶ is halo.

7. The compound according to claim 6, wherein R⁶ is —

Cl or —

Br.

8. The compound according to claim 7, wherein R⁶ is Br.

9. The compound according to claim 5, wherein R⁶ is —

B(OR⁷)₂, and each R⁷ is hydrogen.

10. The compound according to claim 2, wherein the compound of Formula II has the structure:

11. A compound of Formula III-a:

12. The compound according to claim 11, wherein X^A is halo.

13. The compound according to claim 12, wherein X^A is —

Cl or —

Br.

14. The compound according to claim 11, wherein the compound of Formula III-a has the structure:

15. A process for preparing Compound 1-a:

16. The process according to claim 15, wherein X^A is halo.

17. The process according to claim 15, wherein X^A is —

Cl.

18. The process according to claim 15, wherein R⁷ is —

H.

19. The process according to claim 15, wherein PG¹ is —

SO₂-phenyl or Boc, wherein the phenyl is optionally substituted with alkyl.

20. The process according to claim 19, wherein the phenyl is unsubstituted.

21. The process according to claim 15, further comprising:

c-2) reacting a compound of Formula 4-2;

22. The process according to claim 21, wherein the borylating agent comprises bis-pinacol borane.

23. The process according to claim 21, wherein the borylaying agent comprises 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane.

24. The process according to claim 21, further comprising:

d-2) reacting a compound of Formula VI;

25. The process according to claim 24, wherein R^6a—

X^B is Br₂.

26. The process according to claim 24, further comprising:

e) protecting the compound of Formula 6;