Tipifarnib, NSC-702818, R-115777, Zarnestra

替吡法尼 6-[氨基-(4-氯苯基)-(3-甲基咪唑-4-基)甲基]-4-(3-氯苯基)-1-甲基喹啉-2-酮 Chemical Name: (+)-(R)-6-[1-Amino-1-(4-chlorophenyl)-1-(1-methylimidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methylquinolin-2(1H)-one
CAS No. 192185-72-1, 192185-68-5 (racemate), 192185-70-9 (racemic, diHCl), 192185-69-6 (racemic, fumarate)
项目整合开发状态: Phase III
项目研究机构: Janssen (Originator), National Cancer Institute (Codevelopment)
合成路线:Cyclization of 3-(3-chlorophenyl)-N-phenyl-2-propenamide (I) by means of polyphosphoric acid (PPA) at 100 C gives 4-(3-chlorophenyl)-1,2,3,4-tetrahydroquinolin-2-one (II),which is condensed with 4-chlorobenzoic acid (III) by means of PPA at 140 C to yield 6-(4-chlorobenzoyl)-4-(3-chlorophenyl)-1,2,3,4-tetrahydroquinolin-2-one (IV).The dehydrogenation of (IV) by means of Br2 in bromobenzene at 160 C affords 6-(4-chlorobenzoyl)-4-(3-chlorophenyl)quinolin-2(1H)-one (V),which is methylated with iodomethane and NaOH/benzyltrimethylammonium chloride in THF to provide 6-(4-chlorobenzoyl)-4-(3-chlorophenyl)-1-methylquinolin-2(1H)-one (VI).Condensation of compound (VI) with 1-methylimidazole (VII) by means of butyllithium in THF gives the triaryl carbinol (VIII),which is finally treated with ammonia in THF to afford R-115777.