Piperidin-4-ol → tert-Butyl 4-[N-[7-Chloro-3-methyl-2-(4-hydroxypiperidin-1-yl)methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate

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To a solution of tert-butyl 4-[N-[7-chloro-2-methanesulphonyloxymethyl-3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate (0.230 g, 0.42 mmol) in anhydrous dichloromethane (4 ml) under argon was added a solution of 4-hydroxypiperidine (0.424 g, 4.2 mmol) in anhydrous CH2Cl2 (4 ml). The clear solution was stirred at room temperature for 1.5 hours under argon, then partitioned between ethyl acetate (200 ml) and 5% aqueous sodium carbonate solution (100 ml). The organic layer was washed with 5% aqueous sodium carbonate (100 ml), and dilute brine (100 ml), dried (Na2SO4) and concentrated in vacuo. The residue was triturated with ether to give a white precipitate, which was collected by filtration , washed with ether and dried in vacuo over P2O5 (0.206 g, 89%), mp 208-210° C.; 1H-NMR (DMSO-d6) 1.50 (s, 9H, But), 1.33 (m, 2H), 1.65 (m, 2H), 2.17 (m, 2H), 2.72 (m, 2H), and 3.50 (m, 1H), (piperidine ring protons), 3.24 (s, 1H, C≡CH), 3.57, 3.60 (2×s, 5H, N3-Me , 2-CH2), 4.39 (s, 2H, CH2C≡C), 4.55 (d, J=4.1 Hz, 1H, OH), 4.79 (s, 2H, 6-CH2), 6.78 (d, J=8.9 Hz, 2H, 3′,5′-ArH), 7.72 (d, J=8.9 Hz, 2′,6′-ArH), 7.81, 7.87 (2×s, 2H, 5-H, 8-H); MS (ESI, m/z) 551, 553 [(M+H)+, 100%, 37% rcspectively; Cl isotopic pattern].

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