Sodium Hydroxide → 4-amino-5-cyclopropylquinazolin-2(1H)-one

Participants

Reaction Conditions

Reaction Steps

A solution of 2-amino-6-cyclopropylbenzonitrile (Example 92a) (1.0 eq., 1.0 mmol, 158 mg) and benzoyl isocyanate (90% pure, 1.0 eq., 1.0 mmol, 1.171 g/mL, 140 μL) in dioxane (15 mL) was stirred at room temperature. After 2 hours, the volatiles were removed on a rotary evaporator. The resulting crude N-benzoyl urea was suspended in EtOH (10 mL, 200 proof) and NaOH (2.5 eq., 2.5 mmol, 1N, 2.50 mL) was added. The reaction was heated to 75° C. with stirring for 7 hours. The solvent were evaporated and the residue diluted with water (10 mL). The reaction mixture was acidified with 10% citric acid/water solution and carefully titrated to pH 7-8 with saturated NaHCO3 solution. The precipitated product was collected by vacuum filtration, washing with water. The residue was suspended in EtOH (3 mL, 200 proof) and HCl was added (12.1N, 3 mL). The mixture was heated to 90° C. for 1 hour. The reaction mixture was cooled to room temperature and diluted with water (20 mL), filtered (0.45 μm PTFE frit), and the filtrate concentrated on a rotary evaporator. The residue was further purified by preparative TLC (1000 μm, 10/90 MeOH/DCM) and trituration with methanol at room temperature. The reaction gives 25 mg (12.4%) of the title compound as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 0.802 (m, 2H), 1.086 (m, 2H), 2.345 (m, 1H), 6.922 (d, J=8 Hz, 1H), 7.000 (d, J=8 Hz, 1H), 7.253 (br. s, 1H), 7.397 (t, J=8 Hz, 1H), 8.022 (br. s, 1H), 10.644 (s, 1H). MS 202 (MH+).

Provenance & Evidence