Processes and intermediates for preparing MCL1 inhibitors

Patent metadata

Field	Value
Publication number	US-12410146-B2
Application number	US-202318363585-A
Country	US
Kind code	B2
Filing date	Aug 1, 2023
Priority date	Nov 26, 2019
Publication date	Sep 9, 2025
Grant date	Sep 9, 2025

Abstract

The present disclosure provides methods for preparing MCL1 inhibitors or a salt thereof and related key intermediates.

First claim

What is claimed is:

1. A method comprising preparing a compound of formula 13-D or a salt thereof

by reacting a compound of formula 13-C:

with a corresponding compound of formula 6-L

or a salt thereof, to provide the compound of formula 13-D or the salt thereof, wherein R P is selected from —C(═O)—C 1-6 alkyl, —C(═O)-phenyl, —C(═O)—O—C 1-6 alkyl, —C(═O)—O—C 1-6 alkyl-phenyl, and —C(═O)—O—phenyl;
wherein R 2 is H, R 3 is methyl, R y is H, and R 6 is Cl, and
wherein R n is independently C 1-6 alkyl, or the two R n moieties collectively form a C 2-4 alkyl bridge, wherein said bridge is optionally substituted by one to four C 1-3 alkyl and phenyl.

2. The method of claim 1 , wherein the compound of formula 6-L is

3. A method comprising preparing a compound of formula 13-B or a salt thereof:

by reacting a corresponding compound of formula 13-A:

with a compound of corresponding formula 5-E:

to provide the compound of formula 13-B or the salt thereof; wherein
R 6 is halogen and each R n is independently C 1-6 alkyl, or the two R n moieties join together to form a C 2-4 alkyl bridge, wherein the bridge is optionally substituted by one to four groups independently selected from C 1-3 alkyl and phenyl.

4. The method of claim 3 , wherein the compound of formula 5-E is selected from:

Assignees

• Gilead Sciences Inc

Inventors

• Brak Katrien
• Bullock Kae M
• Cizio Greg
• Dao Kathy
• Dixon Darryl D
• Dunetz Joshua R
• Humphreys Luke D
• Huynh Valerie
• Ischay Michael A
• Johnson Trevor C
• Merit Jeffrey E
• Regens Christopher S
• Standley Eric A
• Steinhuebel Dietrich P
• Su Justin Y
• Wu Tao
• Young Marshall D

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/553

  having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine · CPC title

• C07D513/10 Primary

  Spiro-condensed systems · CPC title

• C07D513/04

  Ortho-condensed systems · CPC title

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title