Reaction Steps
To a stirred suspension of 3-(6-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione hydrogen chloride (0.50 g, 1.5 mmol) and triethylamine (0.29 mL, 2.1 mmol) in THF (12 mL) at 510° C., was added hexyl isocyanate (0.25 g, 1.9 mmol), and the mixture was stirred at room temperature overnight. The mixture was quenched with methanol (1 mL), and the solvent was evaporated. The residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%) to give 1-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-6-ylmethyl]-3-hexyl-urea as an off-white solid (410 mg, 65% yield); HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% H3PO4, grad. to 95/5 in 5 min, kept 5 min, 6.05 min (99.0%); mp, 220-222° C.; 1HNMR (DMSO-d6) 0.85 (t, J=6 Hz, 3H, CH3CH2CH2), 1.24-1.38 (m, 8H, CH2CH2CH2CH2), 2.15-2.20 (m, 1H, CHH), 2.56-3.03 (m, 6H, CHCH2, CH3), 4.30 (d, J=6 Hz, 2H, ArCH2NH), 5.26 (dd, J=6, 11 Hz, 1H, Ch), 5.97 (t, J=5 Hz, 1H, CH2NH), 6.40 (t, J=6 Hz, 1H, ArCH2NH), 7.55-7.89 (m, 3H, Ar), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 13.88, 20.93, 22.05, 23.38, 26.03, 29.94, 30.63, 31.02, 39.35, 42.44, 56.51, 119.96, 123.46, 126.40, 133.81, 139.87, 145.64, 154.36, 157.99, 160.46, 169.47, 172.60. LCMS MH=428; Anal Calcd For C22H29N5O4: C, 61.81; H, 6.84; N, 16.38. Found: C, 61.50; H, 6.82; N, 16.23.
