Reaction Steps
A solution of 2-amino-5-(2-benzyloxy-acetylamino)-N-(2,6-dioxo-piperidin-3-yl)-benzamide (0.26 g, 0.6 mmol) and trimethyl orthoformate (2 mL) and p-toluene sulfonic acid (60 mg) in acetonotrile (10 mL) was heated to reflux for 21 hours. To the mixture, was added water (25 mL) and ether (25 mL). The suspension was filtered and washed with water (50 mL) and ethyl acetate (50 mL) to give 2-benzyloxy-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-6-yl]-acetamide as a white solid (180 mg, 72% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 2.87 min (99.3%); mp: 248-250° C.; 1H NMR (DMSO-d6) δ 2.14-2.16 (m, 1H, CHH), 2.62-2.87 (m, 3H, CH2, CHH), 4.15 (s, 2H, CH2), 4.64 (s, 2H, CH2), 5.49-5.50 (m, 1H, NCH), 7.31-7.41 (m, 5H, Ar), 7.68 (d, J=9 Hz, 1H, Ar), 8.06-8.10 (m, 1H, NH), 8.28 (s, 1H, CH), 8.55 (br, 1H, Ar), 10.24 (s, 1H, NH), 11.16 (s, 1H, NH; 13C NMR (DMSO-d6) δ 23.05, 31.48, 58 (br), 69.87, 72.92, 115.69, 122.15, 127.30, 128.16, 128.28, 128.34, 128.77, 137.98, 138.14, 144.06, 146.48, 160.10, 168.93, 170.43, 172.90; LCMS: MH=421; Anal Calcd for C22H20N4O5: C, 62.85; H, 4.79; N, 13.33. Found: C, 60.60; H, 4.29; N, 12.54.
