合成路线1

The chlorosulfonation of 1-methylnaphthalene (I) with chlorosulfonic acid gives 4-methylnaphthalen-1-ylsulfonyl chloride (II), which is nitrated with nitric and sulfuric acids yielding the 8-nitro derivative (III). The reaction of (III) with benzylamine and K2CO3 affords the corresponding sulfonamide (IV), which is cyclized by hydrogenation with formic and Pd/C giving the methylnaphthosultam (VI). The reaction of (VI) with lithium diisopropylamide (LDA) and CO2 yields the carboxymethyl derivative (VII), which is reduced with NaBH4 and BF3 ethearate affording the 2-hydroxyethyl derivative (VIII). Finally, this compound is condensed with 1-(2-amino-2-oxoethyl)-4-aza-1-azoniabicyclo[2.2.2]octane trifluoromethanesulfonate (IX) by means of trifluromethanesulfonic anhydride in acetonitrile to provide the desired naphthosultam intermediate (X). Compound (XI) is obtained by condensation of quinuclidine (XI) with chloroacetamide (XII) by means of sodium trilfluoromethanesulfonate in refluxing acetonitrile. Alternatively, 4-methylnaphthalen-1-ylsulfonyl chloride (II) can be condensed with diethylamine giving the corresponding sulfonamide (XIII), which is nitrated with nitric and sulfuric acids yielding the 8-nitro derivative (XIV). Finally, this compound is cyclized to the previously reported naphthosultam (VI) by hydrogenation with H2 or potassium formate over Pd/C.