合成路线1

The intermediate sulfonamide (VII) was prepared by two synthetic routes starting from trans 4-(aminomethyl)cyclohexanecarboxylic acid (I). 1.- The N-Boc derivative (II) was converted to the mixed anhydride with ClCOOMe and then reduced to alcohol (III) using NaBH4. Subsequent conversion of (III) to tosylate, followed by reaction with NaN3, provided azide (IV), which was reduced to amine (V) by hydrogenation over PtO2 (1). Coupling of (V) with 1-naphthalenesulfonyl chloride (VI) produced the corresponding sulfonamide, which by further acid deprotection of the Boc group gave (VII). 2.- In a related procedure, amino acid (I) was coupled with sulfonyl chloride (VI) to afford sulfonamide (VIII). The carboxylic acid of (VIII) was activated as the mixed anhydride with ClCOOEt and then treated with ammonia to provide amide (IX). Reduction of this amide with BH3 in THF then furnished intermediate (VII). 3.- Quinazolindione (X) was treated with phosphoryl chloride in the presence of N,N-dimethylaniline to produce 2,4-dichloroquinazoline (XI). Selective amination of (XI) at position 4 with ammonia yielded (XII), which was finally condensed with amine (VII) to afford the title compound, which was isolated as the hydrochloride salt.