A New Efficient Synthetic Process for an Endothelin Receptor Antagonist, Bosentan Monohydrate

A new and efficient synthetic process for the synthesis of an endothelin receptor antagonist, bosentan monohydrate, involves the coupling of p-tert-butyl-N-(6-chloro-5-(2-methoxy phenoxy)-2,2′-bipyrimidin-4-yl)benzenesulfonamide (7) with (2,2-dimethyl-1,3-dioxolane-4,5-diyl)dimethanol (14) as a key...

Full description

Saved in:
Bibliographic Details
Published in:Organic process research & development 2013-08, Vol.17 (8), p.1021-1026
Main Authors: Rebelli, Pradeep, Yerrabelly, Jayaprakash Rao, Yalamanchili, Bharathi Kumari, Kommera, Rajashekar, Ghojala, Venkat Reddy, Bairy, Kondal Reddy
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A new and efficient synthetic process for the synthesis of an endothelin receptor antagonist, bosentan monohydrate, involves the coupling of p-tert-butyl-N-(6-chloro-5-(2-methoxy phenoxy)-2,2′-bipyrimidin-4-yl)benzenesulfonamide (7) with (2,2-dimethyl-1,3-dioxolane-4,5-diyl)dimethanol (14) as a key step. This new process provides desired bosentan monohydrate (1) with better quality and yields. Our new methodology consists of technical innovations/improvements which totally eliminate the probability for the formation of critical impurities such as pyrimidinone 8, dimer impurity 9, and N-alkylated impurity 13 in the final drug substance.
ISSN:1083-6160
1520-586X
DOI:10.1021/op400100s