Morpholine → tert-Butyl 4-[N-[7-Chloro-3-methyl-2-morpholinomethyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

Participants

Reaction Steps

A mixture of tert-butyl 4-[N-[7-chloro-2-methanesulphonyloxymethyl-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl )amino]benzoate (0.193 g, 0.35 mmol), dichloromethane (7 ml), and morpholine (0.304 g, 3.5 mmol) was stirred at room temperature for 6 h under argon. The cloudy reaction mixture was then partitioned between ethyl acetate (200 ml) and 5% aqueous sodium carbonate (80 ml). The organic layer was washed more 5% sodium carbonate (2×80 ml), and brine (80 ml), dried (Na2SO4) and concentrated in vacuo. Purification by column chromatography, on elution with 10% ethyl acetate in dichloromethane, afforded a solid which was triturated with 5% dichloromethane in hexanes. The white solid was collected by filtration, dried in vacuo over P2O5 (0.174 g, 82%), mp 140-143° C.; 1H-NMR (DMSO-d6) 1.50 (s, 9H, But), 2.48, (br s obscured) and 3.55 (br s) (8H, N(CH2CH2)2O), 3.62 (s, 5H, 2-CH2, N3-Me), 3.20 (s(poorly resolved triplet), 1H, C≡CH), 4.39 (s, 2H, CH2C≡C), 4.79 (s, 2H, 6-CH2), 6.78 (d, J=8.7 Hz, 2H, 3′,5′-ArH), 7.72 (d, J=8.7 Hz, 2H, 2′,6′-ArH), 7.80, 7.89 (2×s, 2H, 5-H, 8-H). MS (ESI, m/z) 537, 539 [(M+H)+, 100%, 38% respectively; Cl isotopic pattern].

Provenance & Evidence