Processes for preparing an FGFR inhibitor

Patent metadata

Field	Value
Publication number	US-10899760-B2
Application number	US-202016745418-A
Country	US
Kind code	B2
Filing date	Jan 17, 2020
Priority date	Aug 11, 2015
Publication date	Jan 26, 2021
Grant date	Jan 26, 2021

Abstract

Disclosed herein are processes for preparing 8-(3-(4-acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one and FGFR inhibitor, as well as polymorphs and/or salt forms thereof.

First claim

What is claimed:

1. A process of preparing a compound of formula (I):

comprising:
(A) treating compound of formula (a), where X is a leaving group under elimination reaction conditions, with a base

to provide the compound of formula (I); or
(B) reducing the acetylene bond in compound (b)

to provide the compound of formula (I); or
(C) treating a compound of formula (c) with a reducing agent

to provide the compound of formula (I); or
(D) chlorinating a compound of formula (d)

to provide the compound of formula (I).

2. The process of claim 1 wherein the process comprises treating the compound of formula (a) with a base

to provide the compound of formula (I).

3. The process of claim 1 wherein the process comprises reducing the acetylene bond in compound (b)

to provide the compound of formula (I).

4. The process of claim 1 wherein the process comprises treating a compound of formula (c) with a reducing agent

to provide the compound of formula (I).

5. The process of claim 1 wherein the process comprises chlorinating the compound of formula (d)

to provide the compound of formula (I).

6. The process of claim 2 wherein X is halo, phosphate, mesylate, tosylate, or 1,1,1-trifluoro-N-[(trifluoromethyl)sulfonate.

7. The process of claim 2 wherein the reaction is carried out in an aprotic, polar organic solvent.

8. The process of claim 7 wherein the base is either an organic or an inorganic base.

9. The process of claim 3 wherein the reducing agent is Lindlar catalyst.

10. The process of claim 4 where the reducing agent is sodium borohydride or i-PrMgCl/THF and an organic or inorganic acid.

11. The process of claim 5 wherein the process comprises chlorinating with a chlorinating agent that is N-chlorosuccinimide (NCS), sulfonyl chloride, or sulfuryl chloride.

12. The process of claim 11 wherein the chlorinating agent is NCS, the reaction is carried out in a halogenated hydrocarbon, and in the presence of an organic acid or an organic base.

Assignees

• Principia Biopharma Inc

Inventors

• Zhu Jiang
• Masjedizadeh Mohammad

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07B43/04

  of amino groups · CPC title

• C07B35/06

  Decomposition, e.g. elimination of halogens, water or hydrogen halides · CPC title