反应详情

A mixture of methyl 7-amino-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylate (Intermediate 29, 0.400 g) and 2-bromo-4-fluorobenzenesulfonyl chloride (0.565 g) in pyridine (4 mL) and DCM (12 mL) was stirred at room temperature for 30 minutes. The mixture was diluted with ethyl acetate and washed with aqueous potassium carbonate solution (10%) and brine, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of methanol and DCM, with a gradient of 0-2%. The resultant solid was re-purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, containing 1% triethylamine, with a gradient of 0-100% to give a yellow solid which was again purified by chromatography on silica, eluting with a mixture of DCM and cyclohexane (50%), followed by DCM (100%). The resultant solid was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-30%, to give methyl 7-(2-bromo-4-fluorobenzenesulfonylamino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylate (0.317 g) as a yellow gum.

1. washwashed with aqueous potassium carbonate solution (10%) and brine
2. dry with materialdried (MgSO4)
3. filtrationfiltered
4. concentrationThe filtrate was concentrated in vacuo
5. customthe residue was purified by chromatography on silica
6. washeluting with a mixture of methanol and DCM, with a gradient of 0-2%
7. customThe resultant solid was re-purified by chromatography on silica
8. washeluting with a mixture of ethyl acetate and cyclohexane
9. additioncontaining 1% triethylamine
10. customwith a gradient of 0-100% to give a yellow solid which
11. customwas again purified by chromatography on silica
12. washeluting with a mixture of DCM and cyclohexane (50%)
13. customThe resultant solid was purified by chromatography on silica
14. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-30%