301646-60-6

Upstream product

• 1177447-87-8 4-(2-tert-butoxyethoxy)-5-(2-methoxyphenoxy)-6-chloro-2,2'-bipyrimidine 
• 6292-59-7 4-tert-butylbenzenesulphonamide 
• 1334686-04-2 Trifluoromethanesulfonic acid 4-(2-tert-butoxyethoxy)-6-(4-tert-butylbenzenesulfonylamino)-5-(2-methoxyphenoxy)-pyrimidin-2-yl ester 
• 153435-63-3 2-(tributylstannyl)pyrimidine 
• 1334686-03-1 N-[6-(2-tert-Butoxyethoxy)-2-hydroxy-5-(2-methoxy-phenoxy)-pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide 
• 1334686-10-0 C₂₈H₃₇N₃O₈S₂ 
• 14080-23-0 2-cyanopyrimidine 
• 150726-89-9 (2-methoxyphenoxy)-malonic acid dimethyl ester 
• 57871-18-8 methyl ester of imino-pyrimidine acid 
• 90-05-1 2-methoxy-phenol 
• 7580-85-0 tert-butyl glycidyl ether 
• 150728-12-4 5-(2-methoxyphenoxy)-2-(pyrimidin-2-yl) pyrimidine-4,6(1H, 5H)-dione 
• 150728-13-5 4,6-dichloro-5-(2-methoxyphenoxy)-2,2'-bipyrimidine 

Downstream Products

• 157212-55-0 bosentan monohydrate 

Relevant academic research and scientific papers

PROCESS FOR THE PREPARATION OF BOSENTAN

The present invention provides a novel process for obtaining Bosentan, with few synthesis steps, by coupling the intermediate pyrimidine compound of formula I with the sulfonamide compound of formula II. The use of said efficient process prevents the use of hazardous chemicals and thus it is of considerable interest for obtaining Bosentan in a large industrial scale. The invention also refers to the novel intermediates of formula II and to a process for its production.

Process for the preparation of bosentan

The present invention provides a novel process for obtaining Bosentan, with few synthesis steps, by coupling the intermediate pyrimidine compound of formula I with the sulfonamide compound of formula II. The use of said efficient process prevents the use of hazardous chemicals and thus it is of considerable interest for obtaining Bosentan in a large industrial scale. The invention also refers to the novel intermediates of formula II and to a process for its production.

PROCESS FOR PREPARING BOSENTAN

The present invention relates to a novel intermediate useful in the preparation of bosentan and to processes for the preparation of said intermediate and bosentan. The invention further relates to compositions comprising bosentan prepared according to the processes of the invention and their use in the treatment of endothelin-receptor mediated disorders.

Research and development of a second-generation process for bosentan, an endothelin receptor antagonist

A second-generation manufacturing process from 5-(2-methoxyphenoxy)-[2,2′-bipyrimidine]-4,6-(1H,5H)-dione to bosentan is based on the synthesis and deprotection of the tert-butyl ether of bosentan using available and inexpensive ethylene glycol mono-tert-butyl ether. This new strategy triggered a cascade of process improvements. Isolations are reduced from six to three, and drying operations, from five to two. Process solvents are reduced from six to two. The isolations of two sensitizers are eliminated. Toluene is used in place of methylene chloride. Two aqueous waste streams are eliminated by replacing DMF and ethylene glycol by toluene. Two methanol - isopropyl acetate recrystallizations of bosentan are replaced by the decantation of a suspension of bosentan formate monoethanolate in ethanol - toluene. Finally, the overall yield is increased from 67 to 84% and the final product purity improved from 99.3 to 99.7%.