【药物名称】A-324920
化学结构式(Chemical Structure):
参考文献No.630590
标题:Discovery and SAR of diarylsulfide cyclopropylamide LFA-1/ICAM-1 interaction antagonists
作者:Link, J.T.; Sorensen, B.K.; Liu, G.; Pei, Z.; Reilly, E.B.; Leitza, S.; Okasinski, G.
来源:Bioorg Med Chem Lett 2001,11(8),973
合成路线图解说明:

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.

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