Process for making compounds for use in the treatment of cancer

Patent metadata

Field	Value
Publication number	US-10793541-B2
Application number	US-201916271215-A
Country	US
Kind code	B2
Filing date	Feb 8, 2019
Priority date	Oct 12, 2012
Publication date	Oct 6, 2020
Grant date	Oct 6, 2020

Abstract

Disclosed herein is a process of making a compound of formula I

The compound of formula I is an inhibitor of MEK and thus can be used to treat cancer.

First claim

The invention claimed is:

1. A process for preparing a compound of formula II, comprising deprotecting a compound of formula III

2. The process of claim 1 , wherein the deprotecting comprises: performing hydrogenolysis of the Compound of formula III using H 2 in the presence of a heterogeneous transition metal catalyst or treating the Compound of formula III with: chloroethyl chloroformate in the presence of MeCN; or Na/NH 3 .

3. The process of claim 2 , wherein the hydrogenolysis is in the presence of HCl and/or acetic acid.

4. The process of claim 2 , wherein the heterogeneous transition metal catalyst is Pd/C.

5. A process for preparing a compound of formula II, comprising:
1) reacting a compound of formula VII with a compound of formula VII a to provide a compound of formula VI;

2) reducing the compound of formula VI with a borohydride reducing agent to provide a compound of formula V;

3) deprotecting the azetidinyl ring of the compound of formula V to provide a compound of formula IV;

4) reacting the compound of formula IV with a compound of formula IV a to provide a compound of formula III;

and
5) deprotecting, by hydrogenolysis, the compound of formula III to provide the compound of formula II,

wherein PG is an amino protecting group.

6. The method of claim 5 , wherein the amino protecting group is selected from fluorenylmethyloxycarbonyl (FMoc), benzyloxycarbonyl (CBz) or tert-butoxycarbonyl (BOC).

Assignees

• Exelixis Inc
• Genentech Inc

Inventors

• Naganathan Sriram
• Guz Nathan
• Pfeiffer Matthew
• Sowell C Gregory
• Bostick Tracy
• Yang Jason
• Srivastava Amit
• Anand Neel Kumar

Classifications

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61P43/00

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

• C07D498/04

  Ortho-condensed systems · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title