96619-89-5

The invention belongs to the field of drug synthesis, and provides an alibendol preparation method, which comprises: selecting 2-hydroxy-3-methoxybenzaldehyde as a raw material, selecting an efficientoxidative esterification catalyst, carrying out one-step oxidative esterification to obtain methyl 2-hydroxy-3-methoxybenzoate, carrying out a reaction on the methyl 2-hydroxy-3-methoxybenzoate and allyl bromide under the action of an alkali to generate methyl 2-allyloxy-3-methoxybenzoate, carrying out a para Claisen rearrangement reaction on the methyl 2-allyloxy-3-methoxybenzoate at a high temperature to obtain methyl 2-hydroxy-3-methoxy-5-allylbenzoate, and carrying out an aminolysis reaction in ethanolamine to generate alibendol. Compared with the traditional synthetic process, the new process of the present invention has characteristics of simple synthesis steps, convenient post-treatment and good product quality, and is suitable for industrial production.

A number of 2,3-dimethoxy-5-(fluoroalkyl)-N-[(1-ethyl-2-pyrrolidinyl)methyl] benzamides (with or without a 6-hydroxy group) were synthesized and evaluated as dopamine D2 receptor ligands. The parent acids were synthesized via the Claisen rearrangement of the appropriate O-allyl ethers, which were derived from o-vanillic acid or 2,3-dimethoxysalicylic acid. A decrease in reactivity was found to be characteristic of pentasubstituted benzoates, and difficulties were encountered with the introduction of fluorine onto the ethyl side chains. The (fluoroethyl)- and (fluoropropyl)salicylamides were 5 times more potent than the corresponding benzamides in inhibiting [3H]spiperone binding to the D2 receptor. These (fluoroalkyl)salicylamides are of potential value for in vivo positron emission tomography (PET) studies upon the basis of their relatively selective, high potency binding affinity for the D2 receptor.