Mizolastine, MKC-431, SL-85.0324, Zolistam, Zolistan, Mizolen, Zolim, Mizollen

咪唑斯汀Chemical Name: 2-[N-[1-[1-(4-Fluorobenzyl)-1H-benzimidazol-2-yl]-4-piperidinyl]-N-methylamino]pyrimidin-4(3H)-one; 1-(4-Fluorobenzyl)-2-[4-[N-(3,4-dihydro-4-oxopyrimidin-2-yl)-N-methylamino]piperidin-1-yl]benzimidazole
CAS No. 108612-45-9
项目整合开发状态: Launched-1998
项目研究机构: Sanofi-Aventis (Originator), Angelini (Licensee), Ferrer (Licensee), Mitsubishi Chemical (Licensee)
合成路线:Mizolastine can be obtained by two related ways:1) The condensation of 2-chloro-1-(4-fluorobenzyl)benzimidazole (I) with N-(4-piperidyl)carbamic acid ethyl ester (II) by means of NaOCH3 at 14 C gives N-[1-[1-(4-fluorobenzyl)benzimidazol-2-yl]piperidin-4-yl]carbamic acid ethyl ester (III),which is methylated with methyl iodide and NaH in DMF to yield the corresponding N-methyl derivative (IV).The decarboxylative hydrolysis of (IV) with 48% HBr in acetic acid affords N-[1-[1-(4-fluorobenzyl)benzimidazol-2-yl]piperidin-4-yl]-N-methylamine (V),which is finally condensed with 2-(methylsulfanyl)pyrimidin-4(3H)-one (VI) by heating at 170 C.2) Compound (V) can also be obtained by direct condensation of 2-chloro-1-(4-fluorobenzyl)benzimidazole (I) with 4-(methylamino)piperidine (VII) by means of K2CO3 in refluxing isoamyl alcohol.