2-Chloro-4-(morpholin-4-yl)thieno(3,2-d)pyrimidine → 2-Chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde

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Reaction Steps

Scheme 4 shows the synthesis of 4-(2-chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine 9 starting with formylation at the 7-position of 4-(2-chlorothieno[3,2-d]pyrimidin-4-yl)morpholine 4 (1.0 equiv.) in THF with n-BuLi in hexanes to give 2-chloro-4-morpholinothieno[3,2-d]pyrimidine-6-carbaldehyde 5 after acidification. Reductive amination of aldehyde 5 was accomplished with 4-(methylsulfonyl)piperazin-1-ium chloride 8 and sodium acetate (anhydrous powder) in 1,2-dichloroethane. Trimethyl orthoformate was added and stirred for 6 hours, followed by the addition of sodium triacetoxyborohydride to give 9.

Provenance & Evidence