Amino-pyrimidine skeletal muscle modulators

Patent metadata

Field	Value
Publication number	US-11369565-B2
Application number	US-202016941079-A
Country	US
Kind code	B2
Filing date	Jul 28, 2020
Priority date	Apr 23, 2010
Publication date	Jun 28, 2022
Grant date	Jun 28, 2022

Abstract

Provided are compounds of Formula I:or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, X and mare as defined herein.Also provided is a pharmaceutically acceptable composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof.Also provided are methods of using a compound of Formula I, or a pharmaceutically acceptable salt thereof.

First claim

What is claimed is:

1. A method for preparing a compound of formula (X)

or a salt thereof,
wherein the method comprises reacting a compound of formula (E)

with hydrogen to form a compound of formula (D)

and converting the compound of formula (D) to the compound of formula (X), or the salt thereof.

2. The method of claim 1 , further comprising:
converting a compound of formula (F)

to form the compound of formula (E).

3. The method of claim 2 , wherein the step of converting the compound of formula (F) to form the compound of formula (E) comprises reacting the compound of formula (F) with (diethylamino)sulfur trifluoride (DAST) to form the compound of formula (E).

4. The method of claim 2 , further comprising:
converting a compound of formula (G)

to form the compound of formula (F).

5. The method of claim 4 , wherein the step of converting the compound of formula (G) to form the compound of formula (F) comprises reacting the compound of formula (G) with NaBH 4 to form the compound of formula (F).

6. The method of claim 4 , further comprising:
reacting a compound of formula (H)

with NaIO 4 to form the compound of formula (G).

7. The method of claim 6 , further comprising:
reacting a compound of formula (J)

with 2-chloro-3-fluoropyridine to form the compound of formula (H).

8. The method of claim 1 , wherein the step of converting the compound of formula (D) to the compound of formula (X) comprises reacting the compound of formula (D) with 5-bromo-2-fluoropyrimidine;
followed by reacting the resulting product with di-tert-butyl dicarbonate (Boc 2 O) to form a compound of formula (C)

and converting the compound of formula (C) to the compound of formula (X), or the salt thereof.

9. The method of claim 8 , wherein the step of converting the compound of formula (C) to the compound of formula (X) comprises reacting the compound of formula (C) with 3-cyanopyrrole to form a compound of formula (B)

and converting the compound of formula (B) to the compound of formula (X), or the salt thereof.

10. The method of claim 9 , wherein the step of converting the compound of formula (B) to the compound of formula (X) comprises reacting the compound of formula (B) with hydrogen peroxide to form a compound of formula (A)

and reacting the compound of formula (A) with trifluoroacetic acid to form the compound of formula (X), or the salt thereof.

11. A compound selected from the group consisting of:

12. The compound of claim 11 wherein the compound is

13. The compound of claim 11 wherein the compound is

14. The compound of claim 11 wherein the compound is

15. The compound of claim 11 wherein the compound is

16. The compound of claim 11 wherein the compound is

17. The compound of claim 11 wherein the compound is

18. The compound of claim 11 wherein the compound is

19. The compound of claim 11 wherein the compound is

Assignees

• Cytokinetics Inc

Inventors

• Yang Zhe
• Muci Alex R
• Warrington Jeffrey
• Bergnes Gustave
• Morgan Bradley P
• Chuang Chihyuan
• Romero Antonio
• Collibee Scott
• Qian Xiangping
• Lu Pu-Ping

Classifications

• C07D417/14

  containing three or more hetero rings · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61K9/0034

  Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants · CPC title

• C07D239/42 Primary

  One nitrogen atom (nitro radicals C07D239/30) · CPC title