PNU-109291

(1S)-1-{2-[4-(4-甲氧基苯基)-1-哌嗪基]乙基}-N-甲基-3,4-二氢-1H-异苯并吡喃-6-甲酰胺Chemical Name: (-)-1(S)-[2-[4-(4-Methoxyphenyl)piperazin-1-yl]ethyl]-N-methyl-3,4-dihydro-1H-2-benzopyran-6-carboxamide
CAS No. 187665-60-7
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator)
合成路线:The cyclization of 2-(3-bromophenyl)ethyl alcohol (I) with ethyl 3,3-diethoxypropionate by means of TiCl4 in dichlromethane gives racemic 2-(6-bromo-3,4-dihydro-1H-2-benzopyran-1-yl)acetic acid ethyl ester (III),which is regioselectively hydrolyzed by means of Amano P-30 lipase in apH 7 buffer yielding 2-(6-bromo-3,4-dihydro-1H-2-benzopyran-1(S)-yl)acetic acid (IV).The condensation of (IV) with 1-(4-methoxyphenyl)piperazine (V) by means of diethyl cyanophosphate in dichloromethane affords the acylated piperazine (VI),which is reduced with the complex BH3.THF in THF to 6-bromo-1(S)-[2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl]-3,4-dihydro-1H-2-benzopyran (VII).The reaction of (VII) with trimethylsilyl isocyante (VIII) by means of BuLiDMF gives the crboxamide (IX),which is treated with di-tert-butyl dicarbonate and dimethylaminopyridine (DMAP) in dichloromethane to yield the N,N-bis(tert-butoxycarbonyl) derivative (X).Finally,this compound is treated with an excess of methylamine.