合成路线1

The nitration of 2-(3,4-dichlorophenyl)acetic acid (I) with HNO3 and H2SO4 gives 2-(4,5-dichloro-2-nitrophenyl)acetic acid (II), which is treated with refluxing SOCl2 to yield the corresponding acyl chloride (III). The condensation of (III) with bis(trimethylsilyl)acetylene (IV) by means of AlCl3 in dichloromethane affords 1-(2-nitro-4,5-dichlorophenyl)-4-(trimethylsilyl)-3-butyn-2-one (V), which is submitted to a reductive cyclization by means of Fe/AcOH to provide 5,6-dichloro-2-ethynyl-1H-indole (VI) after desilylation with NaOH in methanol. The condensation of (VI) with methyl 3-bromo-2-methoxy-2-propenoate (VII) by means of Pd(PPh3)4 and CuI in hot DMF yields the penta-2-en-4-ynoic ester (VIII), which is reduced by means of H2 over Lindlar catalyst to obtain, as expected, dienoic ester (IX) as a ZZ/EZ mixture, which is treated directly with a catalytic amount of I2 in refluxing toluene to afford dienoic ester (X) as a single isomer. Alternatively, the reduction of (VIII) to (X) can also be performed with CrSO4 in DMF, however, the yields are low. The hydrolysis of (X) with LiOH in MeOH affords the corresponding carboxylic acid (XI), which is finally condensed with the amine (XII) by means of EDC and HOBT in dichloromethane to provide the target amide.