A practical synthesis of 2-arylamino-6-alkylaminopurines from 2,6-dichloropurine

A practical synthesis of N-[4-(6-cyclobutylamino-9H-purin-2-ylamino)-phenyl]-N-methyl acetamide (QAB205, 5a), an antiasthmatic agent, is described from 2,6-dichloropurine (1) by base-assisted substitution of the 6-chloro substituent with cyclobutylamine (2a) followed by a new trimethylsilyl chloride-catalyzed displacement of the 2-chloro group in intermediate 6-cycbutylamino-2-chloropurine (3a) with an aromatic amine. Both steps can also be carried out in one pot without isolating the intermediate 6-cyclobutylamino-2-chloropurine (3a). The general synthetic utility of this route is demonstrated by synthesizing several 2-arylamino-6-alkylaminopurines (5).