Irtemazole, R-60844

伊替马唑Chemical Name: (?-5-[alpha-(1H-Imidazol-1-yl)benzyl]-2-methyl-1H-benzimidazole
CAS No. 115574-30-6
项目整合开发状态: Phase II
项目研究机构: Janssen (Originator)
合成路线:The cyclization of 3,4-diaminobenzophenone (I) with acetylimidic acid ethyl ester (II) in refluxing methanol gives 5-benzoyl-2-methylbenzimidazole (III),which is reduced with NaBH4 in methanol yielding 5-(alpha-hydroxybenzyl)-2-methylbenzimidazole (IV).Finally,this compound is condensed with imidazole (V) in refluxing acetonitrile.

合成路线:Liarozole fumarate is prepared as shown in Scheme 20970301a.Anisol is reacted with 3-chlorobenzoyl chloride (I) under Friedel-Craft conditions to give (3-chlorophenyl)(4-methoxyphenyl)methanone (II).Nitration of (II) is carried out in dichloromethane at 10 C to yield (III).The methoxy group in (III) is replaced by the amino group by means of NH3 in 2-propanol at 100 C under pressure,giving (IV).By reduction of the keto function of (IV) with sodium borohydride in 2-propanol,the corresponding alcohol (V) is obtained,which upon treatment with 1,1'-carbonyldiimidazole in refluxing dichloromethane yields the imidazolyl compound (VI).Hydrogenation of the nitro group in (VI),followed by cyclization of (VII) in a refluxing mixture of formic acid and 4N hydrochloric acid,gives the benzimidazole derivative (VIII).Finally,the treatment of (VIII) with fumaric acid in ethanol yields liarozole fumarate (IX).