Triethylamine → methyl (1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidin-3-yl)methylcarbamoyl]methyl}-4-fluoro-benzenesulfonylamino)-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylate

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Reaction Steps

EDAC (0.058 g) was added to a stirred solution of methyl (1aRS,7bSR)-5-(2-carboxymethyl-4-fluorobenzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 83, 0.109 g) in DCM (3 mL) and the mixture was stirred at room temperature for 10 minutes. A solution of N—((S)-1-ethylpyrrolidin-3-yl)-N-methylamine dihydrochloride (Intermediate 127, 0.102 g) and triethylamine (0.151 g) in DCM (3 mL) was added and the mixture stirred for 17 hours. The mixture was evaporated in vacuo and the residue was dissolved in dioxane (4 mL) and the mixture was heated at 75° C. for 20 hours. After cooling, the mixture was diluted with DCM and water and filtered through a phase separator. The filtrate was evaporated in vacuo and the residue was combined with an identical reaction carried out earlier. The material was purified by chromatography on silica, eluting with a mixture of methanol and DCM with a gradient of 0-50% to give methyl (1aRS,7bSR)-5-(2-{[((S)-1-ethylpyrrolidin-3-yl)methylcarbamoyl]methyl}-4-fluoro-benzenesulfonylamino)-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylate (0.48 g) as a light brown foam.

Provenance & Evidence