Triethylamine → 1-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-(4-methoxy-phenyl)-urea

4-Methoxyphenyl isocyanate (0.4 g, 2.6 mmol) was added to a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.0 mmol) and triethylamine (0.3 g, 2.8 mmol) in THF (30 mL) at 5-10° C. After 10 minutes, the mixture was stirred at room temperature overnight. The reaction was quenched with methanol (1 mL), and the mixture was concentrated. The residue was stirred with 1N HCl (30 mL) for one hour and then filtered. The solid was slurried with hot ethanol (20 mL) to give 1-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-3-(4-methoxy-phenyl)-urea (0.5 g, 59%) as a white solid: mp 205-207° C.; 1H NMR (DMSO-d6) δ 2.05-2.09 (m, 1H), 2.49-2.65 (m, 2H), 2.84-2.97 (m, 1H), 3.68 (s, 3H, OCH3), 4.70 (d, J=5.7 Hz, 2H, CH2), 5.13-5.20 (dd, J=5.2 and 12.4 Hz, 1H, CH), 6.66 (t, J=5.7 Hz, 1H, NH), 6.79 (d, J=9.0 Hz, 2H, Ar), 7.27 (d, J=9.0 Hz, 2H, Ar), 7.75-7.88 (m, 3H, Ar), 8.59 (a, 1H, NH), 11.65 (s, 1H, NH); 13C NMR (DMSO-d6) δ 21.99, 30.94, 48.86, 55.10, 113.86, 119.50, 121.82, 127.15, 131.59, 133.38, 133.62, 134.70, 140.46, 154.03, 155.45, 167.02, 167.60, 169.84, 172.22; Anal. calcd. for C22H20N4O6: C, 60.55; H, 4.62; N, 12.84. Found: C, 60.43; H, 4.42; N, 12.58.

1. customThe reaction was quenched with methanol (1 mL)
2. concentrationthe mixture was concentrated
3. stirringThe residue was stirred with 1N HCl (30 mL) for one hour
4. filtrationfiltered

ORD 기록

ord-418f8e1f32d84019878735145e15cf23

출처 데이터셋

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08481568B2