Synthesis Of Bosentan

Based on the summary review of the development, kinds and mechanism of resistance of pulmonary hypertension drug, and discussion of research progress for the kind of disease at home and abroad, the synthesis progress of bosentan and its key intermediates have been summarized in the thesis. Bosentan which was first line drug of resistance of pulmonary hypertension has the important meaning for treatment of this kind of disease.By analysis of the synthesis process literature of4,6-dichloro-5-(2-methoxy phenoxy)-2.2’-bipyrimidine (compound3), the process with5-(2-methoxy phenyl)-2(pyrimidin-2-yl] pyrimidin-4,6-(1H,5H)-dione (compound2) as a start material. with phosphorous oxychloride as halogenated reagent, with toluene as solvent was determined. We can produce successfully and repeatly.By analysis of the synthesis process literature of4-(1,1-dimethylethyl)-N-[6-chloro-5-(2-methoxy phenoxy)[2.2’-bipyrimidine]-4-yl] benzene sulfonamide (compound4). the process with4.6-dichloro-5-(2-methoxy phenoxy)-2,2’-bipyrimidine (compound3) as raw material, with potassium hydroxide for string acid agent, with acetone as the solvent was determined. We can produce successfully and repeatly.By analysis of the synthesis process literature of the bosentan last step, the process was optimized, and with4-(1,1-dimethylethyl)-N-[6-chloro-5-(2-methoxy phenoxy)[2,2’-bipyrimidine]-4-yl] benzene sulfonamide (compound4) as raw material, with ethylene glycol sodium base to excess glycol was determined. We can produce successfully and repeatly.Finally, we have done the structure confirmation of the bosentan and4-(1,1-dimethylethyl)-N-[6-chloro-5-(2-methoxy phenoxy)[2.2’-bipyrimidine]-4-yl] benzene sulfonamide (compound4).