反应详情

The starting materials are either commercially available or can be synthesized by methods known in the art. Compounds of formula Ia where X is N can be synthesized starting from the known 3-bromo-8-chloro-imidazo[1,2-a]pyrazine (4). Lumma, Jr., W. C.; Randall, W. C.; Cresson, E. L.; Huff, J. R.; Hartman, R. D.; Lyon, T. F. J. Med. Chem. 1983, 26, 357-363. Meurer, L. C.; Tolman, R. L.; Chapin, E. W.; Saperstein, R.; Vicario, P. P.; Zrada, M. M.; MacCoss, M. J. Med. Chem. 1992, 35, 3845-3857. In accordance to Scheme 1 below, 2-amino-3-chloropyrazine (1) can be reacted with 2-bromo-1,1-dimethoxy-ethane (2) to give 8-chloro-imidazo[1,2-a]pyrazine (3) which can be brominated to give 3-bromo-8-chloro-imidazo[1,2-a]pyrazine (4). Compound 4 can be reacted with an appropriate amine (HNR1R2) either in excess or in the presence of another base, such as diisopropyl ethyl amine, in an appropriate solvent, such as ethanol or butanol, between room temperature to reflux to give compound 5. Compound 5 can than be condensed with 2-methylsulfanyl-4-tributylstannanyl-pyrimidine (6) in the presence of a suitable palladium catalyst to give intermediate 7.

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