2-ButynaMide, N-[4-[(3-broMophenyl)aMino]-6-quinazolinyl]-

590-93-2

169205-78-1

194423-06-8

General procedure for the synthesis of N-(4-((3-bromophenyl)amino)quinazolin-6-yl)but-2-ynamide from 2-butynoic acid and N4-(3-bromophenyl)quinazoline-4,6-diamine: 2-butynoic acid (196 mg, 2.3 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (385 mg, 2.0 mmol ) were dissolved in DMF (5 mL) and stirred at 25 °C for 20 min. Subsequently 6-amino-4-[(3-bromophenyl)amino]quinazoline (316 mg, 1.0 mmol) was added. The reaction mixture was stirred under nitrogen protection at 25 °C for 14 hours. After that, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (206 mg, 1.0 mmol) and 2-butynoic acid (82 mg, 1.0 mmol) were added again and stirring was continued for 8 hours. Next, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (197 mg, 1.0 mmol) and 2-butynoic acid (93 mg, 1.0 mmol) were added for the third time and stirred for another 12 h at 25 °C. After completion of the reaction, the reaction was quenched with water. The resulting yellow precipitate was collected, sonicated with acetone and treated with triethylamine. Finally, it was purified by preparative thin layer chromatography on silica gel using 1:1 EtOAc/acetone as eluent. The target product was isolated as a yellow solid (20 mg, 4.7% yield) with a melting point of 281-283 °C. 1H NMR [(CD3)2SO]: δ 10.97 (brs, 1H, NH), 9.93 (s, 1H, NH), 8.76 (s, 1H, H5), 8.57 (s, 1H, H2), 8.14 (s, 1H, H2'). 7.84-7.76 (m, 3H, H7, H8, H4'), 7.34 (t, J = 8.1 Hz, 1H, H5'), 7.29 (d, J = 7.8 Hz, 1H, H6'), 2.09 (s, 3H, CH3). Mass spectrum (APCI): 383 (100, 81BrMH+), 382 (23, 81BrM+), 381 (95, 79BrMH+). Calculated values for elemental analysis (C18H13N4BrO-0.3HCl-0.6C3H6O): C, 55.69; H, 3.99; N, 13.12%. Measured values: C, 55.67; H, 3.96; N, 12.93%.