Pyridone and aza-pyridone compounds and methods of use

Patent metadata

Field	Value
Publication number	US-10344040-B2
Application number	US-201815905363-A
Country	US
Kind code	B2
Filing date	Feb 26, 2018
Priority date	May 7, 2010
Publication date	Jul 9, 2019
Grant date	Jul 9, 2019

Abstract

Pyridone and aza-pyridone compounds of Formula I are provided, including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

First claim

We claim:

1. A process of preparing a compound of formula 230a having the structure of

or a pharmaceutical salt or isomer thereof,
comprising reacting 2,6-dibromo-4-fluorobenzylacetate and a compound of formula of 167e having the structure of

to form the compound of formula 189a having the structure of

and reacting 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) with a compound of formula 189a to form the compound of formula 230a.

2. The process of claim 1 , wherein the reaction is carried out in the presence of potassium acetate, [bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with CH 2 Cl 2 (PdCl 2 dppf:CH 2 Cl 2 ), or 1,4-dioxane.

3. The process of claim 1 , wherein the reaction is carried out in the presence of cesium carbonate, 1,4-dioxane, Xantphos, or tris(dibenzylideneacetone)dipalladium.

4. A process of preparing a compound having formula of 167e having the structure of

or a pharmaceutical salt or isomer thereof,
comprising reacting sodium ethoxide with a compound of formula 167d having the structure of

to form the compound of formula 167e.

5. The process of claim 4 , further comprising reacting hydrogen and a compound of formula 167c having the structure of

to form the compound of formula 167d having the structure of

6. The process of claim 5 , further comprising reacting bromoacetonitrile and a compound of formula 167b having the structure of

to form the compound of formula 167c having the structure of

7. The process of claim 6 , further comprising reacting sodium azide and a compound of formula 167a having the structure of

to form the compound of formula 167b having the structure of

8. The process of claim 7 , further comprising reacting 2-chloro-4,4-dimethylcyclopent-1-enecarbaldehyde and ethoxycarbonylmethylene triphenylphosphorane to form the compound of formula 167a having the structure of

9. A compound having the structure of

10. The compound of claim 9 , wherein the compound is

11. The compound of claim 9 , wherein the compound is

12. The compound of claim 9 , wherein the compound is

13. The compound of claim 9 , wherein the compound is

14. A compound obtained by the process of claim 1 .

15. A compound obtained by the process of claim 4 .

16. A compound obtained by the process of claim 7 .

Assignees

• Gilead Connecticut Inc
• Genentech Inc

Inventors

• Barbosa Antonio J M
• Blomgren Peter A
• Currie Kevin S
• Krishnamoorthy Ravi
• Kropf Jeffrey E
• Lee Seung H
• Mitchell Scott A
• ORTWINE Daniel
• Schmitt Aaron C
• Wang Xiaojing
• Xu Jianjun
• Young Wendy
• Zhang Honglu
• Zhao Zhongdong
• Zhichkin Pavel E

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title