Formamidine acetate → 7-Benzyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4(4aH)-one

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Reaction Steps

Various N-substituted-7-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine derivatives are prepared using a general procedure described below. Accordingly, ethyl 1-benzyl-3-oxopiperidine-4-carboxylate hydrochloride is reacted with formamidine acetate to yield 7-benzyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4(4aH)-one, which, in turn, is reacted with POCl3 to afford the 4-chloro derivative. The intermediate chloro derivative is then condensed with substituted aniline or amine to give the desired N-substituted-7-benzyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine. Debenzylation using standard procedures known in the art followed by nucleophilic displacement of an appropriate 2-halo-pyridine yields the appropriate N-substituted-7-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine. As a representative example, synthesis of N-(4-tert-butylphenyl)-7-(3-chloropyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-amine is depicted in Scheme 1.

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