合成路线1

Several related syntheses for AA-193 have been reported: 1) The Friedel-Crafts' condensation of 2,5-dichlorophenol (I) with benzoyl chloride (II) by means of AlCl3 gives 2,5-dichloro-4-hydroxybenzophenone (III), which by reaction with hydroxylamine and KOH is converted to 5-chloro-6-hydroxy-3-phenylbenzisoxazole (IV). The condensation of (IV) with allyl bromide (V) by means of K2CO3 affords the 7-allyl derivative (VI), which is cyclized by means of N-bromosuccinimide and NaOH to 5-chloro-7-(hydroxymethyl)-3-phenyl-7,8-dihydrofuro[2,3-g]-1,2-benzisox azole (VII). Finally, this compound is oxidized to the final product with KMnO4 in refluxing dichloromethane. 2) The chlorination of 1,3-dimethoxybenzene (VIII) with SO2Cl2 gives 1-chloro-2,4-dimethoxybenzene (IX), which is condensed with benzoyl chloride (II) as before, yielding 5-chloro-2,4-dihydroxybenzophenone (X). Tosylation of (X) with tosyl chloride gives the corresponding ditosyl derivative (XI), which by reaction with hydroxylamine is converted to the oxime (XII). Finally, this compound is treated with KOH in order to cyclize to the benzisoxazole (IV). 3) The reaction of the benzisoxazole (IV) with formaldehyde and dimethylamine gives 5-chloro-7-(dimethylaminomethyl)-6-hydroxy-3-phenylbenzisoxazole (XIII), which is condensed and cyclized with the ylide (XIV) to yield the ethyl ester of the desired product (XV). Finally, this compound is hydrolyzed with NaOH.