Process for making beta 3 agonists and intermediates

Patent metadata

Field	Value
Publication number	US-11708371-B2
Application number	US-202117155982-A
Country	US
Kind code	B2
Filing date	Jan 22, 2021
Priority date	Oct 27, 2011
Publication date	Jul 25, 2023
Grant date	Jul 25, 2023

Abstract

The present invention is directed to processes for preparing beta 3 agonists of Formula (I) and Formula (II) and their intermediates. The beta 3 agonists are useful in the treatment of certain disorders, including overactive bladder, urinary incontinence, and urinary urgency.

First claim

What is claimed is:

1. A process of making a compound of formula (I-21):

comprising reacting the compound of I-7:

with a compound of formula A-4:

2. A method of increasing the yield of a compound of formula I-8:

relative to the yield of a compound of formula (I-21):

the method comprising adding a compound of formula I-7:

to a compound of formula A-4:

at a temperature of from about 25° C. to about 40° C.

3. The method of claim 2 , further comprising adjusting the pH of the reaction mixture formed by the addition of I-7 to A-4 to a value of 6.5-7.0.

4. The method of claim 2 , wherein the molar ratio of the compound of formula A-4 to the compound of formula I-7 is from about 1:1 to about 1.2:1.

5. The method of claim 2 , further comprising dissolving the compound of formula A-4 in a solvent to form a solution prior to the addition of the compound of formula I-7.

6. The method of claim 5 , wherein the solvent is selected from THF, MTBE, CH 2 Cl 2 , MeCN, toluene, and a mixture comprising two of the foregoing solvents.

7. The method of claim 5 , further comprising adding a base to the solution prior to the addition of the compound of formula I-7.

8. The method of claim 7 , wherein the base is a tertiary amine.

9. The method of claim 8 , wherein the base is N,N-diisopropylethylamine.

10. The method of claim 7 , further comprising adding a salt to the solution prior to the addition of the compound of formula I-7.

11. The method of claim 10 , wherein the salt is a lithium halide.

12. The method of claim 11 , wherein the salt is selected from lithium chloride and lithium bromide.

13. A compound which is:

Assignees

• Merck Sharp & Dohme

Inventors

• Chung John Y L
• Campos Kevin
• Cleator Edward
• Dunn Robert F
• Gibson Andrew
• Hoerrner R Scott
• Keen Stephen
• Lieberman Dave
• Liu Zhuqing
• Lynch Joseph
• Maloney Kevin M
• Xu Feng
• Yasuda Nobuyoshi
• Yoshikawa Naoki
• Zhong Yong-Li

Classifications

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/4196

  1,2,4-Triazoles · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• C07D207/09

  Radicals substituted by nitrogen atoms, not forming part of a nitro radical · CPC title

• C07D263/06

  with hydrocarbon radicals, substituted by oxygen atoms, attached to ring carbon atoms · CPC title