反应详情

To 2-piperidone (149 mg, 1.5 mmol) in THF (1 mL) at 0° C. was added n-butyllithium (2.5 M, 0.60 mL, 1.5 mmol) followed by a solution of (2-chloromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine (150 mg, 0.43 mmol) in THF (1.5 mL). The reaction was heated to reflux for 2 h, cooled to room temperature, quenched with H2O and diluted with ether. The aqueous phase was extracted with ether (3×10 mL) The combined organic phases were washed with brine, dried (MgSO4), concentrated and purified by gradient MPLC (SiO2, 0-20% MeOH/CH2Cl2 with 0.1% NH4OH) to give 133 mg (82%) of the title compound as a yellow oil. 1H NMR (MeOH-d4) δ 7.73 (d, 1H), 7.52 (dd, 1H), 7.71 (d, 2H), 6.98-6.96 (m, 2H), 6.90 (d, 2H), 4.82 (s, 2H), 3.84 (s, 3H), 3.55 (s, 3H), 3.52 (m, 2H), 2.53 (m, 2H), 1.92-1.88 (m, 4H); LC-MS (ESI+; 377 ([M+H]+)).

1. temperatureThe reaction was heated
2. temperatureto reflux for 2 h
3. customquenched with H2O
4. additiondiluted with ether
5. extractionThe aqueous phase was extracted with ether (3×10 mL) The combined organic phases
6. washwere washed with brine
7. dry with materialdried (MgSO4)
8. concentrationconcentrated
9. custompurified by gradient MPLC (SiO2, 0-20% MeOH/CH2Cl2 with 0.1% NH4OH)