1174918-30-9

Upstream product

• 150727-06-3 4-tert-butyl-N-(6-chloro-5-(2-methoxyphenoxy)2,2'-bipyrimidin-4-yl)benzene sulfonamide 
• 174227-14-6 p-tert-butyl-N-[6-hydroxy-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]benzenesulfonamide 
• 1447959-38-7 4-tert-butyl-N-(6-(cyanomethoxy)-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl) benzenesulfonamide 
• 1268612-27-6 C₁₅H₁₁ClN₄O₃ 
• 1448588-53-1 N,N′-(6,6′-(2,3-dihydroxybutane-1,4-diyl)bis(oxy)bis-(5-(2-methoxyphenoxy)-2,2′-bipyrimidine-6,4-diyl))bis-(4-tert-butylbenzenesulfonamide) 
• 1448588-52-0 N,N′-(6,6′-(2,2-dimethyl-1,3-dioxolane-4,5-diyl)bis-(methylene)bis(oxy)bis(5-(2-methoxy phenoxy)-2,2′-bipyrimidine-6,4-diyl))bis(4-tert-butylbenzenesulfonamide) 
• 6292-59-7 4-tert-butylbenzenesulphonamide 
• 150728-12-4 5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl) pyrimidine-4,6(1H, 5H)-dione 
• 14080-23-0 2-cyanopyrimidine 
• 150726-89-9 (2-methoxyphenoxy)-malonic acid dimethyl ester 
• 150728-13-5 4,6-dichloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidine 
• 1632289-55-4 4-tert-butyl-N-[6-(2,3-dihydroxypropoxy)-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl]benzenesulfonamide 
• 1632289-54-3 4-tert-butyl-N-{6-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl}benzenesulfonamide 

Downstream Products

• 147536-97-8 bosentan 

Relevant academic research and scientific papers

An alternate synthesis of bosentan monohydrate, an endothelin receptor antagonist 1

An alternate synthesis of an endothelin receptor antagonist bosentan monohydrate is reported. This new synthetic route involves the coupling of p-tert-butyl-N-[6-chloro-5-(2-methoxy-phenoxy)(2,2′-bipyrimidin)-4-yl] benzene sulfonamide with commercially available raw material (2,2-dimethyl-1,3-dioxolan-4-yl)methanol as the key step. Attractive features of this approach are its versatileness, commercial availability of raw materials, usage of eco-friendly reagents, and it efficiently provides the desired bosentan monohydrate free from reported impurities such as dimer, N-alkylated, and pyrimidinone impurities. Georg Thieme Verlag Stuttgart, New York.

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 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.

New approaches to endothelin receptor antagonist-bosentan

An improved and efficient synthetic process developed for an endothelin receptor antagonist, bosentan monohydrate by condensing a key intermediate 4-tert-butyl-N-(6-hydroxy-5-(2-methoxyphenoxy)-2,2'-bipyrimidine-4-yl) benezenesulfonamide 5 with commercially cheaper chloro acetonitrile and α-halo esters. This synthetic approach efficiently provides highly pure bosentan without formation of the major impurity 2 (dimer) and less than 0.15% of Nalkylated impurity 3 and pyrimidinone impurity 5 in the final product. In the present process upon purification of bosentan monohydrate gave overall yield of 62-65%.

PROCESS FOR PREPARATION OF ENDOTHELIAL RECEPTOR ANTAGONIST (BOSENTAN)

The present invention relates to processes for the preparation of an endothelial receptor antagonist. The present invention particularly relates to synthesis of 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]benzene sulfonamide (bosentan).

IMPROVED AND NOVEL PROCESS FOR THE PREPARATION OF BOSENTAN

The present invention relates to an improved and novel process for the preparation of bosentan compound of formula (1). The present invention also relates to a crystalline form of bosentan and its intermediates.