N,N-Dimethylaniline → 4-Chloro-2-(chloromethyl)quinazoline

(2-Chloromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine: A mixture of 2-chloromethyl-quinazolin-4(3H)-one (256 mg, 1.32 mmol), phosphoryl chloride (1.23 ml, 13.2 mmol) and N,N-dimethylaniline (0.34 ml, 2.64 mmol) in chloroform (10 ml) was heated under reflux for 4 h. The reaction mixture was poured onto ice and extracted by ethyl acetate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel with acetate and hexane (1:1) as eluent, yielding 180 mg of 4-chloro-2-chloromethyl-quinazoline. The intermediate (170 mg, 0.80 mmol) and (4-methoxy-phenyl)-methylamine (131.7 mg, 0.96 mmol) in isopropyl alcohol (5 ml) with concentrated HCl (0.05 ml) was stirred at room temperature overnight. The precipitation was formed and collected by filtration, then washed and dried to give 231 mg (92%) of the title compound. 1H NMR (CDCl3): 7.82 (d, J=8.7 Hz, 1H), 7.59-7.53 (m, 1H), 7.15-7.12 (m, 2H), 7.03-7.00 (m, 2H), 6.95-6.91 (m, 2H), 4.73 (s, 2H), 3.85 (s, 3H), 3.62 (s, 3H).

1. temperaturewas heated
2. temperatureunder reflux for 4 h
3. additionThe reaction mixture was poured onto ice
4. extractionextracted by ethyl acetate
5. customThe solvent was evaporated
6. customthe residue was purified by column chromatography on silica gel with acetate and hexane (1:1) as eluent

ORD record

ord-a6d59d227413437f8688199707e190f5

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08258145B2