Salts and solid form of a BTK inhibitor

Patent metadata

Field	Value
Publication number	US-10456403-B2
Application number	US-201816116425-A
Country	US
Kind code	B2
Filing date	Aug 29, 2018
Priority date	Feb 21, 2014
Publication date	Oct 29, 2019
Grant date	Oct 29, 2019

Abstract

Disclosed herein are processes for preparing 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile free base (compound (I)), salts of compound (I) and solid state form of said salts. Also disclosed herein are pharmaceutical compositions comprising such salts and solid state form thereof and methods of treating cancer, autoimmune, and inflammatory diseases using compound (I) or a pharmaceutically acceptable salt thereof.

First claim

What is claimed:

1. A sulfonic acid or carboxylic acid salt of at least one compound selected from (E) isomer, (Z) isomer, and a mixture of (E) and (Z) isomer of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]-pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile.

2. The sulfonic acid or carboxylic acid salt of the at least one compound of claim 1 , wherein the salt is a sulfonic acid salt.

3. The sulfonic acid salt of the at least one compound of claim 2 , wherein the sulfonic salt is mono- or di-methanesulfonic acid salt.

4. An amorphous form of a pharmaceutically acceptable salt of at least one compound selected from (E) isomer, (Z) isomer, and a mixture of (E) and (Z) isomer of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]-pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile.

5. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 4 , wherein the pharmaceutically acceptable salt is a sulfonic acid or a carboxylic acid salt.

6. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 4 , wherein the pharmaceutically acceptable salt is a sulfonic acid salt.

7. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 6 , wherein the sulfonic acid salt is mono- or di-methanesulfonic acid salt.

8. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 4 , wherein the amorphous form is substantially free of any crystalline form(s) of the pharmaceutically acceptable salt of the at least one compound.

9. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 4 , wherein at least about 90% w/w of the pharmaceutically acceptable salt of the at least one compound is in amorphous form.

10. The sulfonic acid or carboxylic acid salt of the at least one compound of claim 1 , wherein the salt of the at least one compound is a substantially pure E or Z isomer.

11. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 4 , wherein the salt of the at least one compound is a substantially pure E or Z isomer.

12. The sulfonic acid or carboxylic acid salt of the at least one compound of claim 10 , wherein at least about 80% w/w of the salt of the at least one compound is the E isomer.

13. The sulfonic acid or carboxylic acid salt of the at least one compound of claim 10 , wherein at least about 90% w/w of the salt of the at least one compound is the E isomer.

14. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 11 , wherein at least about 80% w/w of the pharmaceutically acceptable salt of the at least one compound is the E isomer.

15. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 11 , wherein at least about 90% w/w of the pharmaceutically acceptable salt of the at least one compound is the E isomer.

16. A pharmaceutical composition comprising:
the sulfonic acid or carboxylic acid salt of the at least one compound of claim 1 ; and
a pharmaceutically acceptable excipient.

17. A pharmaceutical composition comprising:
the amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 4 ; and
a pharmaceutically acceptable excipient.

Assignees

• Principia Biopharma Inc

Inventors

• Masjedizadeh Mohammad Reza
• Gourlay Steven

Classifications

• C07C309/04

  containing only one sulfo group · CPC title

• C07C59/265

  Citric acid · CPC title

• C07C55/06

  Oxalic acid · CPC title

• A61K47/38

  Cellulose; Derivatives thereof · CPC title

• A61K47/10

  Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers · CPC title