合成路线1

Nucleophilic aromatic substitution of 2-chloro-3-nitropyridine (II) with excess piperazine (I) in acetonitrile at room temperature produces 1-(3-nitro-2-pyridyl)piperazine. Protection of the free piperazine nitrogen by treatment with di-tert-butyldicarbonate affords nitropyridine (III). Reduction of the nitro group to the amine is accomplished via hydrogenation (40 psi) over palladium on carbon. Treatment of the aminopyridine with acetaldehyde and sodium cyanoborohydride in methanol affords the (ethylamino)pyridine (IV). Removal of the BOC protecting group with trifluoroacetic acid and coupling of the resulting 1-[3-(ethylamino)pyridyl]piperazine with 5-methoxyindole-2-carboxylic acid using 1-ethyl-3-(dimethylaminopropyl)carbodiimide (EDC) or 1,1'-carbonyldiimidazole (CDI) affords U-87201 (V). Dissolution of (V) in methanol, treatment with 1 eq of methanesulfonic acid, and the addition of diethyl ether results in the precipitation of atevirdine mesylate.