N,N-Dimethylaniline → 2-(4-bromo-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)-5-chlorobenzonitrile

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Reaction Steps

POBr3 (1.61 g, 5.6 mmol) was added portionwise over 2 min to a mixture of 5-chloro-2-(4-hydroxy-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrile (0.82 g, 2.8 mmol), N,N-dimethylaniline (0.7 mL), and N,N-dimethylformamide (0.02 mL) in acetonitrile (10 mL) and anisole (10 mL). The mixture was heated under reflux for 2.5 h and LC-MS showed reaction was complete. After cooling the mixture was diluted with chloroform (20 mL) and poured into a stirred mixture of ice (50 g), 50% KOH (8 mL) and chloroform (100 mL). The organic layer was separated and the aqueous layer was extracted with chloroform (25 mL×2). The combined organic layers were washed with brine (100 mL), dred (Na2SO4), filtered and concentrated. The residue was purified by silica gel column to yield a brown solid (0.35 g).

Provenance & Evidence