4-Aminobenzoic Acid → HCID 52109435, compound

Participants

Reaction Steps

A mixture of 2,4-dichloroquinazoline (200 mg, 1.00 mmol) and morpholine (131 mg, 1.50 mmol) in dimethylformamide (1 mL) was stirred at rt for 5 min. The reaction mixture was diluted with ethyl acetate, washed with saturated sodium bicarbonate and 5% aqueous lithium chloride and dried over sodium sulfate. The solvent was removed on a rotary evaporator to give a white solid. A mixture of this material and 4-aminobenzoic acid (119 mg, 0.868 mmol) in n-butanol (2.5 mL) was heated to 135° C. until the butanol was boiled off. The solid residue was collected and washed with water to give 4-(4-morpholinoquinazoline-2-ylamino)benzoic acid (303 mg, 100%) an off-white solid that was used without further purification. This material was combined with 2,6-dimethylaniline (210 mg, 1.73 mmol), Hunig's base (300 μL, 1.72 mmol) and HATU (329 mg, 0.865 mmol) in DMF (5 mL), and the mixture was heated to 65° C. overnight. The reaction was cooled to rt, diluted with ethyl acetate and extracted with water. The organic layer was washed with saturated sodium bicarbonate and concentrated on a rotary evaporator. The resulting residue was purified by preparative reverse phase HPLC to give N-(2,6-dimethylphenyl)-4-[(4-morpholin-4-ylquinazolin-2-yl)amino]benzamide (120 mg, 26%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.50 (bs, 1H), 9.70 (bs, 1H), 8.05-8.01 (m, 3H), 7.83-7.79 (m, 3H), 7.63 (d, 1H), 7.40 (t, 1H), 7.13 (s, 3H), 3.97 (bs, 4H), 3.84-3.82 (m, 4H), 2.19 (s, 6H). MS (EI) for C27H27N5O2: 454.0 (MH+).

Provenance & Evidence