Processes for the preparation of an apoptosis-inducing agent

Patent metadata

Field	Value
Publication number	US-9199992-B2
Application number	US-201514644970-A
Country	US
Kind code	B2
Filing date	Mar 11, 2015
Priority date	Mar 13, 2013
Publication date	Dec 1, 2015
Grant date	Dec 1, 2015

Abstract

Provided herein is a process for the preparation of an apoptosis-inducing agent, and chemical intermediates thereof. Also provided herein are novel chemical intermediates related to the process provided herein.

First claim

What is claimed is:

1. A process for the preparation of a compound of formula (C):

wherein R is C 1 to C 12 alkyl, which comprises:
(a) combining a compound of formula (A):

with R 1 MgX in an aprotic organic solvent; wherein R 1 is C 1 to C 6 alkyl and X is Cl, Br or I; and
(b) combining a C 1 to C 12 alkyl chloroformate or a di-(C 1 to C 12 alkyl)dicarbonate with the product of step (a), to provide the compound of formula (C).

2. The process of claim 1 wherein R is selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, iso-butyl and neo-butyl.

3. The process of claim 1 wherein R 1 is isopropyl.

4. The process of claim 1 wherein R is ethyl and the C 1 to C 12 alkyl chloroformate is ethyl chloroformate.

5. The process of claim 1 wherein R is tert-butyl and the di-(C 1 to C 12 alkyl)dicarbonate is di-tert-butyl dicarbonate.

6. A compound of the formula:

7. A process for the preparation of the compound of claim 6 , wherein the process comprises:
(x) combining a compound of formula (B):

with a compound of formula (C):

wherein R is tert-butyl,
and a tert-butoxide salt in an organic solvent to provide the compound of claim 6 .

8. A compound of the formula:

9. A process for the preparation of the compound of claim 8 , wherein the process comprises:
(y) combining a compound of formula (B):

with a compound of formula (C):

wherein R is tert-butyl,
and a tert-butoxide salt in an organic solvent to provide the compound of formula (D):

wherein R is tert-butyl;
(z) combining the compound of formula (D), wherein R is tert-butyl;

with a compound of formula (I):

a source of palladium, a tert-butoxide salt, and a phosphine ligand in an aprotic organic solvent to provide the compound of claim 8 .

Assignees

• Abbvie Inc

Inventors

• Chan Vincent S
• Christesen Alan C
• Grieme Timothy A
• Ku Yi-Yin
• Mulhern Mathew M
• Pu Yu-Ming M

Classifications

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07C69/78

  Benzoic acid esters · CPC title

• C07C67/10

  by reacting carboxylic acids or symmetrical anhydrides with ester groups or with a carbon-halogen bond (preparation from carboxylic acid halides C07C67/14) · CPC title

• C07C67/00

  Preparation of carboxylic acid esters · CPC title

• C07C69/76

  Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring · CPC title