Morpholine → (R)-1-(4-Fluorophenyl)-4a-methoxymethyl-6-(5-morpholin-4-ylpyridine-3-sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triazacyclopenta[b]naphthalene

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Reaction Conditions

Reaction Steps

A mixture of (R)-6-(5-bromopyridine-3-sulfonyl)-1-(4-fluorophenyl)-4a-methoxymethyl-4,4a,5,6,7,8-hexahydro-1H-1,2,6-triazacyclopenta[b]naphthalene (0.15 g), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.035 g), tris(dibenzylideneacetone)dipalladium (0.026 g), sodium tert-butoxide (0.049 g), morpholine and tetrahydrofuran was heated at 100° C. in a microwave reactor for 30 minutes. The mixture was filtered through Celite, and the pad was washed with ethyl acetate. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (4:1 by volume), to afford a yellow oil. The yellow oil was purified by preparative reverse-phase HPLC, eluting with a mixture of methanol and water containing 0.1% formic acid (9:20 to 4:3 by volume) to afford the title compound as a white solid (0.097 g). LCMS (Method C): 540 (M+H)+, Retention time 10.6 minutes.

Provenance & Evidence