【药物名称】ORG-25935
化学结构式(Chemical Structure):
参考文献No.42228
标题:Aminomethylcarboxylic acid derivs.
作者:Jaap, D.R.; Gilfillan, R.; Gibson, S.G.; Thorn, S.N. (Akzo Nobel N.V.)
来源:EP 1100769; WO 0007978
合成路线图解说明:

Conjugate addition of methyl acrylate (II) to 3-methoxybenzaldehyde (I) under reversion of reactivity conditions in the presence of KCN produced the keto ester (III). The Wolff-Kishner reduction of the keto group caused simultaneous ester hydrolysis, yielding acid (IV), which was further cyclized to the tetralone (V) employing hot polyphosphoric acid. Mannich reaction of ketone (V) with N-benzyl methylamine and paraformaldehyde furnished amino ketone (VI). To this was added phenylmagnesium bromide (VII), yielding amino alcohol (VIII), which was subsequently dehydrated to (IX) by means of trifluoroacetic acid. Catalytic hydrogenation of the olefin double bond of (IX) with simultaneous N-benzyl group hydrogenolysis gave the secondary amine (X). This was then alkylated with ethyl bromoacetate, producing the substituted glycine ester (XI), which was finally hydrolyzed by means of LiOH.

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