Diisopropylethylamine → N-(3-amino-5-isoquinolinyl)-N'-[3-fluoro-4-(trifluoromethyl)benzyl]urea

Participants

Reaction Conditions

Reaction Steps

2-Fluoro-4-(isocyanatomethyl)-1-(trifluoromethyl)benzene (2.59 mmol) in toluene (10 mL) was treated with N-(5-amino-3-isoquinolinyl)acetamide (400 mg, 1.99 mmol) and DIEA (1.8 mL). The mixture was heated at 80° C. for 5 hours, cooled to room temperature, and filtered. The solid was triturated with 97:3 CH2Cl2:CH3OH and stirred as a suspension in 48% aqueous HBr (8 mL) at 60° C. for 2 hours. After cooling to room temperature, the mixture was poured into concentrated NH4OH (20 mL). The solid was washed with water and air-dried to provide the title compound. The corresponding hydrochloride salt was prepared by treatment with methanolic HCl. 1H NMR (300 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.68 (s, 1H), 7.94 (s, 1H), 7.76 (t, 1H, J=7.9 Hz), 7.35-7.49 (m, 3H), 7.26 (s, 1H), 7.09 (s, 1H), 6.92 (s, 1H), 6.84 (t, 1H, J=6.0 Hz), 6.62 (s, 1H), 4.41 (d, 2H, J=6.1 Hz).

Provenance & Evidence