反应详情

To a stirred solution of the aldehyde (5-8, 2.01 g, 5.15 mmol, 1 equiv) and N-methanesulfonylpiperazine acetic acid salt (4.62 g, 20.60 mmol, 4 equiv) in dichloroethane (400 mL) was added at ambient temperature acetic acid (1.2 mL). The reaction mixture was treated with sodium triacetoxyborohydride and stirred for 3 h. The reaction stopped at 76% of conversion and treated with MgSO4 and additional 1 g of the hydride. After further stirring for 1 h the reaction was complete. The reaction mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3. The organic layer was once again washed with saturated aqueous NaHCO3, and then with brine, separated, dried with (Na2SO4) and concentrated in vacuo. The crude solid was dissolved in dimethylformamide and treated with the activated carbon. The filtrate solution (celite) was concentrated to syrup which was quickly trituated with methanol (100 mL). The resulting solid was collected by filtration, redissolved in dimethylformamide, concentrated to syrup, trituated with methanol (100 mL), collected by filtration and vacuum-dried to give 5-(4-Methanesulfonyl-piperazin-1-ylmethyl)-2-(2-oxo-1,2-dihydro-quinolin-3-yl)-indole-1-carboxylic acid tert-butyl ester (5-9) as a white powder; 1H NMR (500 MHz, DMSO-d6) δ12.06 (s, 1H), 8.06 (s, 1H), 8.04 (d, 1H, J=8.5 Hz), 7.74 (d, 1H, J=8.0 Hz), 7.55 (s, 1H), 7.53 (dt, 1H, J=8.0, 1.5 Hz), 7.35 (d, 1H, J=8.5 Hz), 7.30 (dd, 1H,J=8.5, 1.5Hz), 7.22 (t, 1H, J=7.5 Hz), 6.76 (s, 1H), 3.62 (s, 2H), 3.16 (m, 4H), 2.87 (s, 3H), 2.48 (m, 4H), 1.35 (s, 9H).

1. stirringAfter further stirring for 1 h the reaction
2. customThe reaction mixture was partitioned between ethyl acetate and saturated aqueous NaHCO3
3. washThe organic layer was once again washed with saturated aqueous NaHCO3
4. customwith brine, separated
5. dry with materialdried with (Na2SO4)
6. concentrationconcentrated in vacuo
7. dissolutionThe crude solid was dissolved in dimethylformamide
8. additiontreated with the activated carbon
9. concentrationThe filtrate solution (celite) was concentrated to syrup which
10. filtrationThe resulting solid was collected by filtration
11. dissolutionredissolved in dimethylformamide
12. concentrationconcentrated to syrup
13. filtrationcollected by filtration
14. customvacuum-dried