3,4-Dimethylphenyl isocyanate → 3-(3,4-dimethyl-phenyl)-1-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-1-methyl-urea
反応式
Cl.[O:2]=[C:3]1[CH:8]([N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][C:15]=3[CH2:19][NH:20][CH3:21])[C:10]2=[O:22])[CH2:7][CH2:6][C:5](=[O:23])[NH:4]1.[CH3:24][C:25]1[CH:26]=[C:27]([N:32]=[C:33]=[O:34])[CH:28]=[CH:29][C:30]=1[CH3:31]>C(Cl)Cl>[CH3:24][C:25]1[CH:26]=[C:27]([NH:32][C:33](=[O:34])[N:20]([CH2:19][C:15]2[CH:14]=[CH:13][CH:12]=[C:11]3[C:16]=2[C:17](=[O:18])[N:9]([CH:8]2[CH2:7][CH2:6][C:5](=[O:23])[NH:4][C:3]2=[O:2])[C:10]3=[O:22])[CH3:21])[CH:28]=[CH:29][C:30]=1[CH3:31]参加物
4
反応物 2
生成物 1
試薬・触媒・溶媒 1
実験手順
To a suspension of 2-(2,6-dioxo-piperidin-3-yl)-4-methylaminomethyl-isoindole-1,3-dione hydrochloride (0.65 g, 1.93 mmol) and 3,4-dimethylphenyl isocyanate (0.32 mL, 2.31 mmol) in dry CH2Cl2 (80 ml), was added diidopropylethylamine (0.47 mL g, 2.60 mmol). The mixture was stirred at room temperature overnight. The reaction mixture was quenched with MeOH (1 mL). The suspension was filtered, and the resulting solid cake was rinsed with CH2Cl2 (5 ml). The solid was reslurried with ether (I 5 mL) to give 3-(3,4-dimethyl-phenyl)-1-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-1-methyl-urea as a solid (0.51 g, 59%)): mp 202-204° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=6.23 (99%); 1H NMR (DMSO-d6): δ 2.14 (s, 3H), 2.16 (s, 3H), 2.54-2.64 (m, 2H), 2.85-2.97 (m, 1H), 3.03 (s, 3H), 5.00 (s, 2H), 5.14-5.20 (dd, J=5.3, 12.6 Hz, 1H), 6.99 (d, J=8.2 Hz, 1H), 7.19 (d, J=8.1 Hz, 1H), 7.26 (s, 1H), 7.61 (d, J=7.2 Hz, 1H), 7.89-7.81 (m, 2H), 8.34 (s, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 18.62, 15.54, 21.97, 30.91, 35.10, 47.46, 48.85, 117.61, 121.43, 121.83, 127.54, 129.12, 129.51, 131.78, 132.42, 134.95, 135.63, 137.93, 138.97, 155.79, 16696, 167.58, 169.80, 172.74. Anal Calcd for C24H24N4O5: C, 64.28; H, 5.39; N, 12.49. Found: C, 63.99; H, 5.26; N, 12.39.