Process for making beta 3 agonists and intermediates

Patent metadata

Field	Value
Publication number	US-10087189-B2
Application number	US-201715808740-A
Country	US
Kind code	B2
Filing date	Nov 9, 2017
Priority date	Oct 27, 2011
Publication date	Oct 2, 2018
Grant date	Oct 2, 2018

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):

comprising (a) mixing compound I-11:

with a salt of compound

in an aqueous or non-aqueous solvent, and adding an acid and a coupling agent;
wherein the coupling agent is selected from the group consisting of CDI, DCC, EDC, EDC methiodide, T3P, HATU, HBTU and mixed-anhydrides; and
wherein the solvent is selected from the group consisting of MeOH, EtOH, IPA, n-PrOH, MeCN, DMF, DMAc, and a combination thereof.

2. The process of claim 1 , wherein the salt of compound

is a Na + , Li + , K + , Cs + , Ca 2+ , Ba 2+ , or Mg 2+ salt.

3. The process of claim 1 , wherein the salt of compound

is a Na + salt.

4. The process of claim 1 , wherein the coupling agent comprises EDC.

5. The process of claim 1 , wherein the acid is HCl.

6. The process of claim 1 , wherein the solvent is an aqueous solvent.

7. The process of claim 1 , wherein the solvent is IPA.

8. The process of claim 1 , wherein the process further comprises (b) adding aqueous ammonia to the reaction mixture of step (a) to form a slurry.

9. The process of claim 8 , wherein the process further comprises (c) aging the slurry before filtration.

10. A process of making a compound of Formula (I):

comprising (a) mixing compound I-11:

with compound i-12 in an aqueous solvent, and adding HCl and a coupling agent comprising EDC, wherein the solvent is selected from the group consisting of MeOH, EtOH, IPA, n-PrOH, MeCN, DMF, DMAc, and a combination thereof;

(b) adding aqueous ammonia to the reaction mixture of step (a) to form a slurry; and
(c) aging the slurry before filtration.

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

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P13/10

  of the bladder · CPC title

• C07D263/06

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

• C07D207/09

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

• A61K31/4196

  1,2,4-Triazoles · CPC title