Process for preparing beta 3 agonists and intermediates

Patent metadata

Field	Value
Publication number	US-10696681-B2
Application number	US-201916298467-A
Country	US
Kind code	B2
Filing date	Mar 11, 2019
Priority date	Mar 15, 2013
Publication date	Jun 30, 2020
Grant date	Jun 30, 2020

Abstract

The application is directed to efficient and economical processes as described in more detail below for the preparation of the beta 3 agonists of the formula of I-7 and intermediate compounds that can be used for making these agonists. The present disclosure relates to a process for making beta-3 agonists and intermediates using ketoreductase (KRED) biocatalyst enzymes and methods of using the biocatalysts.

First claim

What is claimed is:

1. A crystalline form of the HCl salt of Compound I-5(b), wherein Compound I-5(b) has the chemical structure:

and wherein the crystalline form is characterized by an XRPD pattern having 2θ peaks at about 8.6°, 13.5°, and 16.7° 20.9°, and 22.7°.

2. The crystalline form of claim 1 , wherein the crystalline form is characterized by an XRPD pattern having 2θ peaks at about 8.6°, 12.9°, 13.5°, 16.7°, 20.9°, 22.7°, and 24.4°.

3. The crystalline form of claim 1 , wherein the crystalline form is characterized by an XRPD pattern having 2θ peaks at about 4.2°, 8.6°, 12.9°, 13.5°, 16.7°, 20.9°, 22.7°, 24.4°, 24.7°, and 28.2°.

4. The crystalline form of claim 1 , wherein the crystalline form is characterized by an XRPD pattern as shown in FIG. 1 .

5. The crystalline form of claim 1 , wherein the crystalline form is characterized by an XRPD pattern having the following reflections with the d-spacing

Position [°2 Theta]
d-spacing [Å]

4.2174
20.95196

8.5827
10.3028

12.9282
6.84784

13.5177
6.55051

16.65
5.32461

20.9425
4.24193

22.6974
3.91777

24.363
3.65356

24.6986
3.60468

28.1911
3.16555.

Assignees

• Merck Sharp & Dohme

Inventors

• Xu Feng
• Liu Zhuqing
• Desmond Richard
• Park Jeonghan
• Kalinin Alexei
• Kosjek Birgit
• Strotman Hallena
• Li Hongmei
• Moncecchi Johannah

Classifications

• C07C215/30

  containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• C07D207/08

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

• C07D207/12

  Oxygen or sulfur atoms · CPC title

• C12P17/10

  Nitrogen as only ring hetero atom · CPC title