反应详情

A mixture of 5-(2-chloro-ethoxy)-2-methyl-1H-indole-3-carboxylic acid benzyl ester (Example 1, Step A, 0.400 g, 1.16 mmol), 3-pyrrolidin-2-yl-pyridine (0.345 mL, 2.33 mmol), K2CO2 (0.322 g, 2.33 mmol), and KI (0.019 g, 0.116 mmol) in 23 mL of acetonitrile was heated at reflux for 24 hours. The reaction mixture was cooled to room temperature, diluted with CH2Cl2 (50 mL) and washed with water (2×20 mL). The organic layer was dried over MgSO4 and concentrated to give a brown oil. The product was purified by flash column chromatography on silica gel (3% methanol:CH2Cl2) and triturated with diethyl ether/hexanes/CH2Cl2 to give 0.120 g (23.0%) of a light yellow solid: mp 126-127° C.; IR (KBr)3036, 2962, 2793, 1693, 1594, 1454, 1168, 1077 cm−1; 1HNMR (400 MHz, DMSO-d6) δ 1.40-1.52 (m, 1H, NCHCH2CH2CH2), 1.70-1.85 (m, 2H, NCHCH2CH2CH2 & NCHCH2CH2CH2), 2.10-2.18 (m, 1H, NCHCH2CH2CH2), 2.29-2.31 (m, 1H, NCHCH2CH2CH2),2.34-2.42 (m, 1H, NCHCH2CH2CH2), 2.46 (s, 3H, CCH3), 2.71 (t, J=6.35 Hz, 2H, OCH2CH2), 3.38-3.42 (m, 1H, NCHCH2CH2CH2), 3.82 (t, J=5.62 Hz, 2H, OCH2CH2), 5.26 (s, 2H, OCH2Ar), 6.64 (dd, J=8.79, 2.44 Hz, 1H, ArH), 7.17 (t, J=8.55 Hz, 1H, ArH), 7.28 (t, J=7.08 Hz, 3H, ArH), 7.35 (t, J=7.33 Hz, 2H, ArH), 7.46 (d, J=7.81 Hz, 2H, ArH), 7.73 (d, J=7.81 Hz, 1H, ArH), 8.39-8.40 (m, 1H, ArH), 8.51 (s, 1H, ArH), 11.70 (s, 1H, NH); MS(APCI+): m/z 456.2 (MH+). Anal. Calcd for C28H29N3O3: C, 73.79; H, 6.42; N, 9.22. Found: C, 73.42; H, 6.45; N, 9.11.

1. temperaturewas heated
2. temperatureat reflux for 24 hours
3. washwashed with water (2×20 mL)
4. dry with materialThe organic layer was dried over MgSO4
5. concentrationconcentrated
6. customto give a brown oil
7. customThe product was purified by flash column chromatography on silica gel (3% methanol:CH2Cl2)
8. customtriturated with diethyl ether/hexanes/CH2Cl2