Thionyl Chloride → HCID 10616889, compound

Participants

Reaction Steps

A heterogeneous mixture of 6-fluoropyrido[3,4-d]pyrimidin-4(3H)-one (93) (4.0 g, 24.2 mmol), thionyl chloride (100 mL) and a catalytic amount of DMF (3 drops) was stirred under reflux for 1 h. The resulting solution was evaporated under reduced pressure at 45° C. (bath temperature) to give a light brown solid. To this solid was added a mixture of 3-bromo-4-fluoroaniline (5.1 g, 26.8 mmol) and dry DMA (25 mL). The reaction mixture was stirred at room temperature for 40 min, then a 5% solution of sodium bicarbonate (250 mL) was added and the mixture was stirred at room temperature for 15 min. The precipitated solid was collected by filtration and washed successively with water and hexane several times, before being dried under vacuum over silica gel to give N-(3-bromo-4-fluorophenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine (162) (8.13 g, 99%), mp 275-277° C. (literature mp 269-270° C.; Smaill et al. J Med Chem, 1999, 42, 1803-1815); 1H NMR δ [(CD3)2SO] 10.12 (s, 1H), 8.97 (s, 1H), 8.74 (s, 1H), 8.32 (dd, J=6.4, 2.6 Hz, 1H), 8.23 (poorly resolved d, J=0.8 Hz, 1H), 7.93-7.87 (m, 1H), 7.46 (t, J=8.8 Hz, 1H). Anal. Calcd for C13H7BrF2N4: C, 46.32; H, 2.09; N, 16.62%. Found C, 46.54; H, 3.33; N, 16.42%.

Provenance & Evidence