Sodium hydride → HCID 46183671, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-[2-(5,8-difluoroquinazolin-4-ylamino)-ethyl]-2-methoxyphenol (3.73 g, 11.25 mmol) in DMF (25 mL) in a dry 250 mL round bottom flask equipped with a dry nitrogen line and a magnetic stir bar was added sodium hydride (324 mg, 13.5 mmol). After gas evolution had subsided, 2-fluoro-5-trifluoromethyl-pyridine (2.05 g, 12.3 mmol) was added, and the reaction mixture was stirred at 25° C. After 20 h, additional sodium hydride (50 mg, 2.1 mmol) and 2-fluoro-5-trifluoromethyl-pyridine (100 mg, 0.6 mmol) were added. After 20 min, the reaction mixture was quenched by addition of sat. aq. NH4Cl (30 mL) and concentrated in vacuo. The residue was suspended in water (50 mL) and stirred vigorously to break up chunks. The solid product was collected by suction filtration and washed on the filter with water. The filter cake again was suspended in water (50 mL) and stirred vigorously to break up chunks. The solid product was collected by suction filtration and washed with water. The filter cake was dried with suction on the filter overnight to provide 5.26 g (98% yield) of (5,8-difluoroquinazolin-4-yl)-{2-[3-methoxy-4-(5-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-amine as an off-white powder, M.P. 119-121° C. LC-MS: 477 (M++1); 1H NMR (CDCl3): δ 8.69 (s, 1H), 8.4 (m, 1H), 7.89 (dd, 1H), 7.36 (m, 1H), 7.12 (m, 1H), 7.01 (m, 2H), 6.93 (m, 2H), 6.78 (bd, 1H), 3.97 (m, 2H), 3.75 (s, 3H), 3.06 (m, 2H).

Provenance & Evidence