反应详情

温度

0 °C

TEA (0.28 g, 2.8 mmol) was added to a stirred mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methanesulfonate (0.50 g, 1.4 mmol) and chlorobenzoyl chloride (0.25 g, 1.4 mmol) in acetonitrile (30 ml) at 0° C. The mixture was stirred at 0° C. for 2 h, and then 4% aqueous HCl (30 ml) was added. The solid precipitate was filtered and dried in vacuo providing 2-chloro-N-[2,6-dioxo-piperidin-3yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-benzamide as a white solid, (0.33 g, 59% yield); mp 194-196° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 ml/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 3.33 (99.10%); 1H NMR (DMSO-d6) δ 1.98-2.04 (m, 1H), 2.33-2.43 (m, 1H), 2.46-2.63 (m, 1H), 2.86-2.98 (m, 1H), 4.33 (d, 1H, J=17.4 Hz), 4.46 (d, 1H, J=17.4 Hz), 4.57 (d, 2H, J=6.0 Hz), 5.12 (dd, 1H, J=13.2 Hz, J=5.1 Hz), 7.38-7.53 (m, 5H), 7.58 (s, 1H), 7.71 (d, 1H, J=7.8 Hz), 9.09 (t, 1H, J=6.0 Hz), 10.99 (s, 1H); 13C NMR (DMSO-d6) δ 22.5, 31.2, 40.3, 42.5, 47.1, 51.6, 122.1, 122.9, 127.1, 127.2, 128.9, 129.6, 130.4, 130.8, 136.7, 142.4, 143.4, 166.5, 167.9, 170.9, 172.9; LCMS: MH=412, 414; Anal. Calcd for C21H18ClN3O4+0.1H2O: C, 60.98; H, 4.43; N, 10.16. Found: C, 60.76; H, 4.40; N, 10.11.

1. filtrationThe solid precipitate was filtered
2. customdried in vacuo