Processes and intermediates for preparing mcl1 inhibitors

Patent metadata

Field	Value
Publication number	US-2024109851-A1
Application number	US-202318363585-A
Country	US
Kind code	A1
Filing date	Aug 1, 2023
Priority date	Nov 26, 2019
Publication date	Apr 4, 2024
Grant date	—

Abstract

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

First claim

1 - 24 . (canceled)

25 . A method comprising preparing the compound of formula 9-B:

or the salt thereof, by reacting a corresponding compound of formula 13-D

to provide the compound of formula 9-B or the salt thereof, wherein the compound of formula 13-D is prepared by reacting a compound of formula 13-C:

or a salt thereof, with a corresponding compound of formula 6-L

or a salt thereof, to provide the compound of formula 13-C 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 x is H, R y is H, R 5 is methyl, 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.

26 . The method of claim 25 , wherein the compound of formula 6-L is

or a salt thereof.

27 . The method of claim 25 , further comprising preparing a compound of formula 13-B:

or a salt thereof, by reacting a corresponding compound of formula 13-A:

or a salt thereof, with a compound of corresponding formula 5-E:

to provide the compound of formula 13-B or the salt thereof.

28 . The method of claim 27 , wherein the compound of formula 5-E is selected from:

29 - 34 . (canceled)

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

• C07C2602/28

  Hydrogenated naphthalenes · CPC title

• C07C2601/04

  with a four-membered ring · CPC title