Crystalline solid forms of a BET inhibitor

Patent metadata

Field	Value
Publication number	US-11091480-B2
Application number	US-202016828031-A
Country	US
Kind code	B2
Filing date	Mar 24, 2020
Priority date	Jun 20, 2016
Publication date	Aug 17, 2021
Grant date	Aug 17, 2021

Abstract

The present application relates to crystalline solid forms of an inhibitor of BET proteins such as BRD2, BRD3, BRD4, and BRD-t, including methods of preparation thereof, and intermediates in the preparation thereof, where the compound is useful in the treatment of diseases such as cancer.

First claim

What is claimed is:

1. A process of preparing Compound 7:

comprising reacting Compound 6:

with 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) in the presence of P3 and B3, wherein P3 is a transition metal catalyst and B3 is a base.

2. The process of claim 1 , wherein B3 is an alkali metal acetate base.

3. The process of claim 1 , wherein the reacting of Compound 6 with 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) is carried out in a third solvent.

4. The process of claim 1 , wherein the reacting of Compound 6 with 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) is carried out at a temperature of about 70° C. to about 90° C.

5. A compound which is

or a salt thereof.

6. The compound of claim 5 , wherein Compound 7 is a salt thereof.

7. The process of claim 1 , wherein P3 is a palladium catalyst.

8. The process of claim 7 , wherein the palladium catalyst is [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II).

9. The process of claim 7 , wherein the palladium catalyst is selected from [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), dichloro(bis{di-tert-butyl[4-(dimethylamino)phenyl]-phosphoranyl})palladium (Pd-132), Pd(PPh 3 ) 4 , and tetrakis(tri(o-tolyl)phosphine)palladium(0).

10. The process of claim 2 , wherein the alkali metal acetate base is potassium acetate.

11. The process of claim 1 , wherein about 0.01 to about 0.05 equivalent of P3 is used based on 1 equivalent of Compound 6.

12. The process of claim 1 , wherein about 3 to about 3.5 equivalent of B3 are used based on 1 equivalent of Compound 6.

Assignees

• Incyte Corp

Inventors

• Chen Shili
• Jia Zhongjiang
• Liu Pingli
• Qiao Lei
• Wu Yongzhong
• Zhou Jiacheng
• Li Qun

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07F5/025

  Boronic and borinic acid compounds · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · 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