反应详情

5-(2-Chloro-ethoxy)-2-methyl-1H-indole-3-carboxylic acid benzyl ester (0.400 g, 1.163 mmol, 1 eq, Example 1, Step A) was suspended in dry acetonitrile (50 mL) under Ar. K2CO3 (0.320 g, 2.32 mmol, 2 eq) and KI (0.020 g, 0.116 mmol, 0.1 eq) were added followed by the addition of 3-(dimethylamino)pyrrolidine (0.198 g, 1.740 mmol, 1.5 eq). The reaction mixture was stirred and heated to reflux for 3 days. Then the reaction was quenched with saturated sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic phases were washed with brine and dried over Na2SO4. After removing the solvent, the residue was loaded on silica gel and chromatographed, eluting with ethyl acetate/methanol/triethyl amine (100/10/1). 0.270 g (55%) of the indole-pyrrolidine was obtained as a white solid. This was converted to the .2HCl salt. LC/MS (ESI+) 422 (M+1); Anal. Calcd for C25H31N3O3.2HCl.2H2O.0.25AcOEt: C, 56.52; H, 7.11; N, 7.61; Found: C, 56.50; H,. 6.73; N, 7.23.

1. temperatureheated
2. temperatureto reflux for 3 days
3. customThen the reaction was quenched with saturated sodium bicarbonate
4. extractionextracted with ethyl acetate (3×)
5. washThe combined organic phases were washed with brine
6. dry with materialdried over Na2SO4
7. customAfter removing the solvent
8. customchromatographed
9. washeluting with ethyl acetate/methanol/triethyl amine (100/10/1)