Diisopropylethylamine → 2-(2-((2S)-2-((6-(benzyloxy)-3-oxa-8-azabicyclo[3.2.1]oct-8-yl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol

Participants

Reaction Conditions

Reaction Steps

A 20-mL vial was charged with 6-(benzyloxy)-8-(((2S)-4-(2-thiophenylsulfonyl)-2-piperazinyl)methyl)-3-oxa-8-azabicyclo[3.2.1]octane (endo) (250 mg, 0.54 mmol), 2-(2-chloropyrimidin-5-yl)-1,1,1-trifluoropropan-2-ol (244 mg, 1.078 mmol, Intermediate E), Hünig's base (0.29 mL, 1.62 mmol) and dioxane (5 mL). The reaction was heated to 120° C. for 12 h. The mixture was then concentrated onto silica gel and purified via column chromatography (120 g silica gel, 0 to 100% EtOAc in hexanes) to give 2-(2-((2S)-2-((6-(benzyloxy)-3-oxa-8-azabicyclo[3.2.1]oct-8-yl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol (endo) (170 mg) as a mixture of four isomers.

Provenance & Evidence