合成路线1

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.