Synthesis of heterocyclic compounds

Patent metadata

Field	Value
Publication number	US-11739088-B2
Application number	US-202117243358-A
Country	US
Kind code	B2
Filing date	Apr 28, 2021
Priority date	Apr 29, 2020
Publication date	Aug 29, 2023
Grant date	Aug 29, 2023

Abstract

Provided herein are intermediates and processes useful for facile synthesis of compounds of Formula 2:wherein R1 is C(O)R2; R2 is alkyl optionally substituted with 1-5 halogens; G is phenyl or a 5-6 membered heteroaryl optionally substituted with 1-2 R3; and each R3 is independently C1-C6 alkyl, CN, C1-C6 alkyl-CN, 3-6 membered cycloalkyl, or 4-6 membered heterocycloalkyl.

First claim

What is claimed is:

1. A compound of Formula 2:

or a salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein:
R 1 is C(O)R 2 ;
R 2 is alkyl optionally substituted with 1-5 halogens;
G is phenyl or a 5-6 membered heteroaryl optionally substituted with 1-2 R 3 ; and
each R 3 is independently C 1 -C 6 alkyl, CN, C 1 -C 6 alkyl-CN, 3-6 membered cycloalkyl, or 4-6 membered heterocycloalkyl.

2. A method for preparing a compound of Formula 2:

or a salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, said method comprising:
contacting a compound of Formula (I) or a salt thereof:

with an acetic anhydride, or a derivative thereof, to form the compound of Formula 2, wherein
R 1 is C(O)R 2 ;
R 2 is alkyl optionally substituted with 1-5 halogens;
G is phenyl or a 5-6 membered heteroaryl optionally substituted with 1-2 R 3 ; and
each R 3 is independently C 1 -C 6 alkyl, CN, C 1 -C 6 alkyl-CN, 3-6 membered cycloalkyl, or 4-6 membered heterocycloalkyl.

3. The method according to claim 2 , wherein the acetic anhydride is trifluoroacetic anhydride.

4. A method for preparing a compound of Formula 3:

or a salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, comprising:
contacting a compound of Formula (I) or a salt thereof:

with an acetic anhydride, or a derivative thereof, to form the compound of Formula 2 according to claim 2 ; and
refluxing a compound of Formula 2 with an acetic anhydride, or a derivative thereof, in a suitable solvent to form a compound of Formula 3.

5. The method according to claim 4 , wherein the acetic anhydride is trifluoroacetic anhydride.

6. The method according to claim 4 , wherein the suitable solvent is acetonitrile.

7. A method for preparing a compound of Formula 4:

or a salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, comprising:
contacting a compound of Formula (I) or a salt thereof:

with an acetic anhydride, or a derivative thereof, to form the compound of Formula 2 according to claim 2 ;
refluxing a compound of Formula 2 with an acetic anhydride, or a derivative thereof, in a suitable solvent to form a compound of Formula 3 or a salt thereof

and
reducing a compound of Formula 3 to form a compound of Formula 4.

8. A method for preparing a compound of Formula 5:

or a salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, comprising:
contacting a compound of Formula (I) or a salt thereof:

with an acetic anhydride, or a derivative thereof, to form the compound of Formula 2 according to claim 2 ;
refluxing a compound of Formula 2 with an acetic anhydride, or a derivative thereof, in a suitable solvent to form Formula 3 or a salt thereof

reducing a compound of Formula 3 to form a compound of Formula 4 or a salt thereof

and
combining a compound of Formula 4 with a compound of Formula 6 or a salt thereof:

with a suitable coupling agent to form a compound of Formula 5.

9. The method according to claim 8 , wherein the acetic anhydride is trifluoroacetic anhydride.

10. The method according to claim 8 , wherein the suitable solvent is acetonitrile.

11. The method according to claim 8 , wherein the suitable coupling agent is BOP, PyBOP, PyBrOP, TBTU, HBTU, HATU, COMU, or TFFH.

12. The method according to claim 11 , wherein the suitable coupling agent is PyBOP.

13. A compound of Formula 2a:

or a salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof.

14. A compound of Formula 2e:

or a salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof.

Assignees

• Plexxikon Inc

Inventors

• Lin Jack
• Walters Jason

Classifications

• C07D401/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D213/75

  Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07D213/76 Primary

  to which a second hetero atom is attached (nitro radicals C07D213/61) · CPC title