Processes and intermediates for preparing MCL1 inhibitors

Patent metadata

Field	Value
Publication number	US-11760736-B2
Application number	US-202217701404-A
Country	US
Kind code	B2
Filing date	Mar 22, 2022
Priority date	Nov 26, 2019
Publication date	Sep 19, 2023
Grant date	Sep 19, 2023

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 converting a compound of formula 10-E, or a salt thereof, to a compound of formula 9-B, or a salt thereof:

wherein R 2 and R 3 are independently H or C 1-6 alkyl;
R 5 is C 1-6 alkyl;
R 6 is halogen;
wherein R x and R y are each independently H or C 1-6 alkyl; and
wherein R p is H.

2. The method of claim 1 , further comprising converting a compound of formula 10-C, or a salt thereof to the compound of formula 10-E, or a salt thereof:

3. The method of claim 1 , wherein 10-E is selected from

or a salt thereof.

4. A method comprising converting a compound of formula 10-B, or a salt thereof to a compound of formula 10-E, or a salt thereof:

wherein R p is H;
wherein R y is H;
wherein R 2 and R 3 are independently H or C 1-6 alkyl; and
wherein R 6 is halogen; and
wherein 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.

5. The method of claim 1 , wherein R 2 is H.

6. The method of claim 1 , wherein R 3 is methyl.

7. The method of claim 1 , wherein R 5 is methyl.

8. The method of claim 1 , wherein R 6 is chloro.

9. The method of claim 4 , wherein R 2 is H.

10. The method of claim 4 , wherein R 3 is methyl.

11. The method of claim 4 , wherein R 6 is chloro.

12. A method of preparing formula 10-B comprising reacting formula 10-A, or a salt thereof with formula 5-E, or a salt thereof:

wherein 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;
wherein R p is H;
wherein R y is H;
wherein R 2 and R 3 are independently H or C 1-6 alkyl; and
wherein R 6 is halogen.

13. The method of claim 12 , wherein R 2 is H.

14. The method of claim 12 , wherein R 3 is methyl.

15. The method of claim 12 , wherein R 6 is chloro.

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