Thionyl Chloride → HCID 86663607, compound

Participants

Reaction Steps

A suspension of 6-fluoropyrido[3,4-d]pyrimidin-4(3H)-one (93) (6.64 g, 40.2 mmol), thionyl chloride (150 mL) and a catalytic amount of DMF (5 drops) was stirred under reflux for 30 min to give a homogeneous mixture which 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-ethynylaniline (6.56 g, 44.2 mmol) and dry DMA (40 mL). The reaction mixture was then stirred at room temperature for 40 min before a 5% solution of sodium bicarbonate (500 mL) was added and the resultant mixture was stirred at room temperature for 15 min. The solid was collected by filtration and washed several times with water and then hexane, respectively. The solid was then dried under vacuum over silica gel to give N-(3-ethynylphenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine (164) (10.5 g, 99%), mp 225-227° C.; 1H NMR δ [(CD3)2SO] 10.06 (s, 1H), 8.96 (s, 1H), 8.74 (s, 1H), 8.28 (poorly resolved d, J=0.6 Hz, 1H), 8.10 (t, J=1.7 Hz, 1H), 7.95-7.90 (m, 1H), 7.46 (t, J=7.9 Hz, 1H), 7.32-7.27 (m, 1H), 4.22 (s, 1H). Anal. Calcd for C15H9BrFN4: C, 68.18; H, 3.43; N, 21.20%. Found C, 67.80; H, 3.50; N, 20.81%.

Provenance & Evidence