反应详情

A mixture of methyl 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonylamino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylate (Intermediate 27, 0.311 g) and lithium hydroxide monohydrate (0.526 g) in dioxane (10 mL) and water (2.5 mL) was irradiated in the microwave at 135° C. for 45 minutes. After cooling, the mixture was diluted with methanol and acidified with formic acid. The mixture was concentrated in vacuo and the residue was diluted with ethanol and toluene and again concentrated in vacuo. The residue was triturated with methanol in DCM (20% solution) 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 0-20%. The resultant solid was triturated with ethyl acetate to give a pale yellow solid which was purified by preparative HPLC (C18), eluting with a mixture of acetonitrile and water, containing 0.1% formic acid with a gradient of 5-70% to give 7-[2-((Z)-3-diethylaminoprop-1-enyl)-4-fluorobenzenesulfonyl-amino]-2,3,9,9a-tetrahydro-1H-pyrrolo[1,2-a]indole-8-carboxylic acid (0.090 g).

1. customwas irradiated in the microwave at 135° C. for 45 minutes
2. temperatureAfter cooling
3. concentrationThe mixture was concentrated in vacuo
4. additionthe residue was diluted with ethanol and toluene
5. concentrationagain concentrated in vacuo
6. customThe residue was triturated with methanol in DCM (20% solution)
7. filtrationfiltered
8. concentrationThe filtrate was concentrated in vacuo
9. customthe residue was purified by chromatography on silica
10. washeluting with a mixture of methanol and DCM with a gradient of 0-20%
11. customThe resultant solid was triturated with ethyl acetate
12. customto give a pale yellow solid which
13. customwas purified by preparative HPLC (C18)
14. washeluting with a mixture of acetonitrile and water
15. additioncontaining 0.1% formic acid with a gradient of 5-70%