4-Chlorobenzoyl chloride → 4-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-benzamide

To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.16 mmol) in CH2Cl2 (60 ml), was added diisopropylethylamine (0.94 mL, 5.4 mmol) and 4-chlorobenzoyl chloride (0.5 g, 2.8 mmol). The mixture was stirred at room temperature overnight and a suspension was obtained. The reaction mixture was quenched with MeOH (1 mL). The suspension was then filtered, and the solid was rinsed with CH2Cl2 (10 mL) to afford 4-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-benzamide as a white solid (0.5 g, 52%): mp, 233-235° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=4.7 min. (99%); 1H NMR (DMSO-d6): δ 2.06-2.11 (m, 1H), 2.53-2.64 (m, 2H), 2.84-2.93 (m, 1H), 4.95 (d, J=5.8 Hz, 2H), 5.15-5.20 (dd, J=5, 12 Hz, 1H), 7.56-7.59 (dd, J=1.7, 6.8 Hz, 2H), 7.72-7.83 (m, 3H), 7.93-7.96 (dd, J=1.8, 6.8 Hz, 2H), 9.23 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 21.97, 30.92, 38.38, 48.86, 121.90, 127.15, 128.45, 129.25, 131.53, 132.65, 133.09, 134.80, 136.28, 139.08, 165.57, 166.94, 167.51, 169.81, 172.74. Anal Calcd for C21H16ClN3O5: C, 59.23; H, 3.79; N, 9.87; Cl, 8.33. Found: C, 59.27; H, 3.42; N, 9.75; Cl, 8.57.

1. customa suspension was obtained
2. customThe reaction mixture was quenched with MeOH (1 mL)
3. filtrationThe suspension was then filtered
4. washthe solid was rinsed with CH2Cl2 (10 mL)

ORDレコード

ord-18b3d4bcc3b8461f98f17d67ef17546a

出典データセット

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08481568B2