Process for the preparation of 4-(8-(2-chlorophenoxy)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)bicyclo[2.2.1]heptan-1-ol and novel intermediates therefor

Patent metadata

Field	Value
Publication number	US-9580420-B2
Application number	US-201514817352-A
Country	US
Kind code	B2
Filing date	Aug 4, 2015
Priority date	Aug 6, 2014
Publication date	Feb 28, 2017
Grant date	Feb 28, 2017

Abstract

A process is provided for preparing 4-(8-(2-chlorophenoxy)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)bicyclo[2.2.1]heptan-1-ol and novel intermediates used in the process. The compound is a 11-beta hydroxysteroid dehydrogenase type I inhibitor which exhibits activity in the treatment of various metabolic diseases.

First claim

What is claimed is:

1. A compound of the structure

2. A compound according to claim 1 of the structure

3. A process for preparing intermediate 1 of the structure

which comprises treating a dialcohol compound of the structure

with an aqueous mineral acid selected from HCl and H 2 SO 4 .

4. A process for preparing Compound 2 of the structure

which comprises subjecting Compound 1 of the structure

to oxidation to form the acid intermediate 2.

5. The process as defined in claim 4 wherein the aldehyde 1a

is formed as an intermediate.

6. The process as defined in claim 4 where the oxidation is carried out in the presence of sodium chlorite, 2,2,6,6-tetramethylpiperidine-N-oxide and sodium hypochlorite.

7. A process for preparing compound 3 of the structure

which comprises reacting the acid

with a hydrazide salt of the structure

and 2-chloro-4,5-dihydro-1,3-dimethyl-1H-imidazoline chloride

at a reduced temperature to form compound 3.

8. The process as defined in claim 7 wherein the reaction is carried out under an inert atmosphere at a temperature within the range from about 0 to about 5° C.

9. A process for preparing compound I of the structure

which comprises treating Compound 3 of the structure

with a carboxylic acid to form compound I.

10. The process as defined in claim 9 wherein the carboxylic acid is benzoic acid and the reaction is carried out at a temperature within the range from about 105 to 110° C.

11. A process for preparing compound I of the structure

which comprises subjecting Compound 1 of the structure

to oxidation to form compound 2

reacting compound 2 with a hydrazide salt of the structure

and 2-chloro-4,5-dihydro-1,3-dimethyl-1H-imidazoline chloride

at a reduced temperature to form the pyridine hydrazide intermediate 3 of the structure

and treating compound 3 with a carboxylic acid to form Compound I.

Assignees

• Bristol Myers Squibb Co
• Bristol-Meyers Squibb Company

Inventors

• Qian Xinhua
• Zhu Keming
• Deerberg Joerg
• Yang Wendy Wangying
• Yamamoto Kana
• Hickey Matthew R

Classifications

• C07C51/29

  with halogen-containing compounds which may be formed in situ · CPC title

• C07C35/29

  being a (2.2.1) system · CPC title

• C07C2102/42

  Chemistry & Metallurgy · mapped topic

• C07D213/77

  Hydrazine radicals · CPC title

• C07C61/13

  having two rings · CPC title