Synthetic route to anti-viral agents

Patent metadata

Field	Value
Publication number	US-10442792-B2
Application number	US-201816132997-A
Country	US
Kind code	B2
Filing date	Sep 17, 2018
Priority date	Jul 18, 2014
Publication date	Oct 15, 2019
Grant date	Oct 15, 2019

Abstract

The invention provides methods of synthesizing a viral protease inhibitor in high yield, without using expensive catalysts or challenging reaction conditions.

First claim

We claim:

1. A composition, comprising:
(i) enantioenriched Compound 1 or a pharmaceutically acceptable salt thereof:

and
(ii)

or a combination thereof.

2. The composition of claim 1 , wherein the composition comprises

3. The composition of claim 1 , wherein the composition comprises

4. The composition of any one of claims 1 - 3 , wherein Compound 1 is prepared by the process depicted in the following scheme:

5. The composition of claim 4 , wherein solvent A is dichloromethane.

6. The composition of claim 4 or 5 , wherein solvent B comprises water.

7. The composition of claim 4 , wherein solvent C comprises acetonitrile.

8. The composition of claim 1 , wherein Compound I has an enantiomeric excess greater than 90%.

9. The composition of claim 1 , wherein Compound I has an enantiomeric excess greater than 95%.

10. The composition of claim 1 , wherein Compound I has an enantiomeric excess greater than 98%.

11. A composition, consisting essentially of:
(i) enantioenriched Compound 1 or a pharmaceutically acceptable salt thereof:

and
(ii)

or a combination thereof.

12. The composition of claim 11 , wherein the composition consists essentially of

and

13. The composition of claim 11 , wherein the composition consists essentially of

and

14. The composition of any one of claims 11 - 13 , wherein Compound 1 is prepared by the process depicted in the following scheme:

15. The composition of claim 14 , wherein solvent A is dichloromethane.

16. The composition of claim 14 or 15 , wherein solvent B comprises water.

17. The composition of claim 14 , wherein solvent C comprises acetonitrile.

18. The composition of claim 11 , wherein Compound I has an enantiomeric excess greater than 90%.

19. The composition of claim 11 , wherein Compound I has an enantiomeric excess greater than 95%.

20. The composition of claim 11 , wherein Compound I has an enantiomeric excess greater than 98%.

21. A composition, consisting of:
(i) enantioenriched Compound 1 or a pharmaceutically acceptable salt thereof:

and
(ii)

or a combination thereof.

22. The composition of claim 21 , wherein the composition consists of

and

23. The composition of claim 22 , wherein the composition consists of

and

24. The composition of any one of claims 21 - 23 , wherein Compound 1 is prepared by the process depicted in the following scheme:

25. The composition of claim 24 , wherein solvent A is dichloromethane.

26. The composition of claim 24 or 25 , wherein solvent B comprises water.

27. The composition of claim 24 , wherein solvent C comprises acetonitrile.

28. The composition of claim 21 , wherein Compound I has an enantiomeric excess greater than 90%.

29. The composition of claim 21 , wherein Compound I has an enantiomeric excess greater than 95%.

30. The composition of claim 21 , wherein Compound I has an enantiomeric excess greater than 98%.

Assignees

• Abbvie Inc

Inventors

• Cink Russell D
• Lukin Kirill A
• Leanna Marvin R
• Pelc Matthew J
• Towne Timothy B
• Welch Dennie S
• Engstrom Kenneth M
• Ravn Matthew M
• Bishop Richard D
• Zhao Gang
• Mei Jianzhang
• Kallemeyn Jeff M
• Hill David R
• Abrahamson Michael J
• Morrill Westin H

Classifications

• C12P41/005

  by esterification of carboxylic acid groups in the enantiomers or the inverse reaction · CPC title

• C07C68/02

  from phosgene or haloformates · CPC title

• C07C2601/08

  the ring being saturated · CPC title

• C07C211/35

  containing only non-condensed rings · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title