A-324920

Chemical Name: 1-[2-[2,3-Dichloro-4-[trans-2-[N-[3-(2-oxopyrrolidin-1-yl)propyl]carbamoyl]cyclopropyl]phenylsulfanyl]phenyl]piperidine-3-carboxylic acid
CAS No. 350592-74-4, 350492-06-7 (diastereomer), 350492-07-8 (diastereomer)
项目整合开发状态: Preclinical
项目研究机构: Abbott (Originator)
合成路线:2,3-Dichloro-4-hydroxybenzaldehyde (I) was converted to the corresponding aryl triflate (II),which was subsequently condensed with 2-bromothiophenol (III),yielding the diaryl sulfide (IV).Wittig reaction of aldehyde (IV) with the ylide resulting from the phosphonium salt (V) afforded the unsaturated ester (VI).Cycloaddition between (VI) and the in situ-generated dimethylsulfoxonium methylide gave rise to the cyclopropane derivative (VII).After basic hydrolysis of the ethyl ester (VII),the resultant carboxylic acid (VIII) was coupled with 1-(3-aminopropyl)-2-pyrrolidinone (IX),providing amide (X).Displacement of the aryl bromide group of (X) with ethyl nipecotate (XI) in the presence of BINAP and Pd catalysts furnished the piperidine-substituted compound (XII).The ethyl ester group of (XII) was finally hydrolyzed to the target carboxylic acid under basic conditions.