反应详情

温度

0 °C

TEA (0.28 g, 2.8 mmol) was added to a mixture of 3-(5-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione methanesulfonate (0.5 g, 1.4 mmol) and 4-chlorobenzoyl chloride (0.25 g, 1.4 mmol) in DMF (30 mL) at 0° C. The mixture was stirred at 0° C. for 2 h, then, 4% aqueous HCl (30 mL) was added. The solid precipitate was filtered and dried in vacuo providing 4-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-benzamide as a white solid (0.22 g, 40% yield); mp 278-280° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 ml/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 3.10 (95.66%); 1H NMR (DMSO-d6) δ 1.97-2.03 (m, 1H), 2.31-2.45 (m, 1H), 2.57-2.62 (m, 1H), 2.85-2.97 (m, 1H), 4.30 (d, 1H, J=17.3 Hz), 4.45 (d, 1H, J=17.3 Hz), 4.59 (d, 2H, J=5.7 Hz), 5.11 (dd, 1H, J=13.2 Hz, J=5.1 Hz), 7.47 (d, 1H, J=8.1 Hz), 7.54-7.58 (m, 3H), 7.70 (d, 1H, J=7.8 Hz), 7.91-7.96 (m, 2H), 9.23 (t, 1H, J=6.0 Hz). 13C NMR (DMSO-d6) δ 22.5, 31.2, 42.8, 47.1, 51.6, 122.1, 122.9, 127.1, 128.4, 129.2, 130.4, 132.9, 136.1, 142.4, 143.7, 165.2, 167.9, 170.9, 172.8; LCMS: MH=412, 414; Anal. Calcd for C21H18ClN3O4+0.5 CH2Cl2: C, 56.84; H, 4.22; N, 9.25. Found: C, 56.79; H, 4.30; N, 9.33.

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