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

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-chloro-2-(4-methoxy-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrile (4.15 g, 13.1 mmol), N,N-dimethylaniline (0.18 mL, 1.4 mmol), N,N-dimethylformamide (0.21 mL, 2.7 mmol) and acetonitrile (35 mL) was heated to dissolve at 105° C. Phosphoryl chloride (5.3 mL, 56 mmol) was added dropwise over 3 mins and the mixture was heated to reflux at 110° C. After another 20 hours refluxing, the reaction mixture was allowed to cool and poured over ice (200 g), and then 45% NaOH (75 mL) was added. The mixture was extracted with CH2Cl2 (3×200 mL). The combined organic layers were dried over sodium sulfate, and concentrated. The residue was purified by silica gel chromatography (0-100% EtOAc/hexane) to afford a yellow oil which became a solid in the freezer.

Provenance & Evidence