6148-18-1

6141-22-6

6148-18-1

General procedure for the synthesis of 2-(chloromethyl)quinazoline from 2-chloro-N-(2-formylphenyl)acetamide: 2-chloro-N-(2-formylphenyl)acetamide (0.869 g, 4.40 mmol) was stirred with a methanol solution of 7 N ammonia (4.4 mL, 30.8 mmol) in a sealed tube for 4.5 h at room temperature. The progress of the reaction was monitored by TLC (9:1 hexane/EtOAc) and it was found that a new point with lower Rf value was generated, but a large amount of feedstock remained unreacted. Subsequently, stirring was continued at room temperature for 19.5 hours, during which a white precipitate was formed. Volatiles were removed under reduced pressure to give a beige solid, which was treated with CHCl3. Examination of the soluble fraction of CHCl3 by TLC (7:3 hexane/EtOAc) revealed that the main component was a new point with an Rf value lower than that of the starting material. The CHCl3 solution was placed in a 0°C refrigerator for the weekend. The insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on an Analogix IF-280 (Agilent SF10-4g, 100% CHCl3) with the product eluting in fractions 1-10. The product-containing fractions were combined and concentrated under reduced pressure to afford 2-(chloromethyl)quinazoline as a white solid (418 mg, 53.2% yield).1H NMR (300 MHz, CDCl3) δ 9.45 (s, 1H), 8.09-8.04 (m, 1H), 7.99-7.92 (m, 2H), 7.70 (ddd, J = 8.0, 6.9 1.2 Hz, 1H), 4.92 (s, 2H).