【药物名称】S-19014
化学结构式(Chemical Structure):
参考文献No.26135
标题:Benzospiroalkene derivs., process for their preparation and pharmaceutical compsns. containing them
作者:Cordi, A.; Lacoste, J.-M.; Laubie, M.; Verbeuren, T.; Descombes, J.-J. (ADIR et Cie.)
来源:CA 2128359; EP 0635497; FR 2709306; JP 1995304753; US 5436261
合成路线图解说明:

Knoevenagel condensation of 3,4-dimethylbenzaldehyde (I) with malonic acid in the presence of piperidine afforded dimethylcinnamic acid (II), which was reduced to the saturated acid (III) by catalytic hydrogenation. Conversion of (III) to the corresponding acid chloride, followed by Friedel-Crafts cyclization, gave rise to the 1-indanone (IV). This was isomerized to the desired 2-indanone (VII) by the sequence of ketone reduction, followed by acidic dehydration of the resulting alcohol to give indene (V), which was converted to epoxide (VI) and then Lewis-acid promoted rearrangement to the 2-indanone (VII). Condensation of ketone (VII) with benzylamine and subsequent addition of trimethylsilyl cyanide to the resulting imine furnished amino nitrile (VIII). After reduction of (VIII) to the diamine (IX) with LiAlH4, the N-benzyl group was removed by transfer hydrogenolysis, yielding (X). Condensation of diamine (X) with formamidine acetate produced the target imidazoline, which was finally isolated as the fumarate salt.

参考文献No.592882
标题:Spiro[(1,3-diazacyclopent-1-ene)-5,2'-(5',6'-dimethylindane)]: A new alpha-adrenergic partial agonist. Two synthetic approaches
作者:Lacoste, J.-M.; Verbeuren, T.J.; Cordi, A.; Descombes, J.-J.; Couchay, C.
来源:16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000,Abst PA-83
合成路线图解说明:

Knoevenagel condensation of 3,4-dimethylbenzaldehyde (I) with malonic acid in the presence of piperidine afforded dimethylcinnamic acid (II), which was reduced to the saturated acid (III) by catalytic hydrogenation. Conversion of (III) to the corresponding acid chloride, followed by Friedel-Crafts cyclization, gave rise to the 1-indanone (IV). This was isomerized to the desired 2-indanone (VII) by the sequence of ketone reduction, followed by acidic dehydration of the resulting alcohol to give indene (V), which was converted to epoxide (VI) and then Lewis-acid promoted rearrangement to the 2-indanone (VII). Condensation of ketone (VII) with benzylamine and subsequent addition of trimethylsilyl cyanide to the resulting imine furnished amino nitrile (VIII). After reduction of (VIII) to the diamine (IX) with LiAlH4, the N-benzyl group was removed by transfer hydrogenolysis, yielding (X). Condensation of diamine (X) with formamidine acetate produced the target imidazoline, which was finally isolated as the fumarate salt.

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