YM-31472

Chemical Name: 2-Butyl-4-(3,N-dimethyl-2-butenamido)-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-ylmethyl]imidazole-5-carboxylic acid 1-(ethoxycarbonyloxy)ethyl ester
CAS No. 149586-24-3
项目整合开发状态: Preclinical
项目研究机构: Yamanouchi (Originator)
合成路线:The reaction of ethyl valerimidate hydrochloride (I) with cyanamide in ethanol yielded cyanoimidate (II),which was converted into the cyanoimidoylglycine (IV) on treatment with glycine ethyl ester (III) and triethylamine.Alkylation of (IV) with the biphenyl derivative (V) in the presence of 1 mole of NaH in DMF gave the intermediate cyanoamidine (VI),which,by further addition of half an equivalent of sodium hydride was cyclized to the imidazole (VII).Acylation of (VII) with 3,3-dimethylacryloyl chloride (VIII) in cold pyridine yielded amide (IX),and then N-alkylation with iodomethane and sodium hydride in DMF provided (X).Acidic treatment with acetic acid in refluxing ethanol removed the trityl group to give (XI).

合成路线:The alkaline hydrolysis of the ester group of (XI) yielded acid (XII).Tetrazole ring was then protected by alkylation with trityl chloride to the trityl derivative (XIII),which was then converted to the potassium salt (XIV) with ethanolic KOH.Alkylation of the potassium salt with 1-iodoethyl ethyl carbonate (XV) in acetone provided the acetaldehyde acylal (XVI),and final deprotection of trityl group with ethanolic acetic acid furnished the target compound (1).