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With chlorosulfonic acid; In chloroform; at 0 - 50℃; for 5.5h; |
To a solution of benzo [cd]indol-2(1H)-one 2 (10g, 60mmol) in chloroform (150mL) was added batches of chlorosulfonic acid (22mL, 6.0 equiv.) at 0C for 30min. The reaction mixture was heated at 50C for 5h. The mixture was then poured into ice water and extracted with CHCl3 (100mL×3). The organic layer was washed with brine and dried over Na2SO4. The solid was filtered off, and the filtrate was concentrated under reduced pressure to afford 2-oxo-1,2-dihydrobenzo [cd]indole-6-sulfonyl chloride (10g, yield 50%). The resulting crude product was resolved in dichloromethane (100mL), then the solution was added into pyrrolidine (3.4mL, 1.2 equiv.) and N-ethyldi isopropylamine (DIPEA, 18mL, 3.0 equiv.). The reaction mixture was stirred at room temperature for 5h. After completion of the reaction as monitored by TLC, dilute HCl was added, the aqueous layer was extracted with DCM (80mL×3), and the organic layer was washed with water and brine, dried with Na2SO4, and evaporated to give 6-(pyrrolidin-1-ylsulfonyl) benzo [cd]indol-2(1H)-one 3 (9g, yield 80%). The product 3 (150mg, 0.5mmol) and sodium hydride (NaH, 36mg, 1.5mmol) were dissolved in DMF (15mL). Bromoethane (65.4mg, 0.6mmol) was added dropwise into the solution and the reaction mixture was stirred at room temperature. After completion of the reaction as monitored by TLC, the reaction mixture was extracted with ethyl acetate (10mL×2). The organic layer was washed with brine and dried over Na2SO4. The solid was filtered off, and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel chromatography with petroleum ether/ethyl acetate (3/1, v/v) to yield compound 1. Under the same conditions, compounds 4-9 were obtained (for detail, see Supporting information 1 and 2). 4.2.1 1-Ethyl-6-(pyrrolidin-1-ylsulfonyl)benzo[cd]indol-2(1H)-one (1) Yellow-green solid, yield 77%, m. p. 168.1-168.9C; 1H NMR (600MHz, CDCl3) delta (ppm): 8.79 (d, J=8.4Hz, 1H), 8.16 (d, J=7.2Hz, 1H), 8.11 (d, J=7.2Hz, 1H), 7.83 (t, J=7.8Hz, 1H), 6.96 (d, J=7.8Hz, 1H), 3.99 (q, J=7.2Hz, 2H), 3.31 (t, J=6.6Hz, 4H), 1.79-1.77 (m, 4H), 1.39 (t, J=7.2Hz, 3H); 13C NMR (150MHz, CDCl3) delta (ppm): 167.6 (C=O), 143.6, 132.9 (CH), 130.4 (CH), 130.3 (CH), 127.0, 126.5, 125.8 (2C), 125.2 (CH), 103.0 (CH), 47.5 (2CH2), 35.1(CH2), 25.3 (2CH2), 13.9 (CH3); HRMS (ESI): Calcd for C17H18N2O3SNa ([M+Na]+): 353.0936, Found: 353.0932. Anal. Calcd for C17H18N2O3S: C, 61.80; H, 5.49; N, 8.48. Found: C, 61.78; H, 5.52; N, 8.49. |