Dimethylformamide → 3-[7-(pyrrolidine-1-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester
반응식
[CH:1]([O:4][C:5]([C:7]1[N:8]([CH:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19](Br)[CH:20]=3)[CH2:15][CH2:14][CH2:13]2)[CH:9]=[N:10][CH:11]=1)=[O:6])([CH3:3])[CH3:2].[NH:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1.CN([CH:31]=[O:32])C>>[CH:1]([O:4][C:5]([C:7]1[N:8]([CH:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([C:31]([N:23]4[CH2:27][CH2:26][CH2:25][CH2:24]4)=[O:32])[CH:20]=3)[CH2:15][CH2:14][CH2:13]2)[CH:9]=[N:10][CH:11]=1)=[O:6])([CH3:3])[CH3:2]참가 물질
4
반응 조건
- 온도
- 100 °C
실험 절차
3-[7-(Pyrrolidine-1-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester and 3-[7-(dimethylcarbamoyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester can be obtained from the reaction mixture resulting from this procedure. A pressure tube fitted with a septum is charged with 3-(7-bromo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester, which can be prepared as described in Example 5, (0.304 g, 0.836 mmol), pyrrolidine (0.298 g, 4.184 mmol), (bis-triphenylphosphine)palladium dichloride (0.029 g, 0.418 mmol), and DMF (4 mL). Carbon monoxide is bubbled through the solution for 15 min, and then the septum is replaced with a screw cap and the mixture is heated to 100° C. overnight. The reaction is cooled to room temperature, diluted with water, and extracted with ethyl acetate. The organic phase is dried over sodium sulfate, filtered, and concentrated. The resulting residue is purified by silica gel chromatography (dichloromethane-methanol mixtures) to give 3-[7-(pyrrolidine-1-carbonyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester; MS: (ESI) m/z 382.2 (M+H)+; 1H NMR (400 MHz, MeOD) δ ppm 1.37 (d, J=6.3 Hz, 3 H), 1.39 (d, J=6.3 Hz, 3 H), 1.85-2.01 (m, 6 H), 2.28-2.33 (m, 2 H), 2.90-2.98 (m, 1 H), 3.09 (dt, J=17.4, 6.3 Hz, 1 H), 3.27-3.33 (m, 1 H), 3.38-3.42 (m, 1 H), 3.56 (t, J=6.9 Hz, 2 H), 5.21 (sept, J=6.3 Hz, 1 H), 6.37 (t, J=5.9 Hz, 1 H), 7.05 (br. s, 1 H), 7.36 (d, J=7.8 Hz, 1 H), 7.45 (dd, J=7.8, 1.5 Hz, 1 H), 7.56 (s, 1 H), 7.76 (s, 1 H); and