Diisopropylethylamine → N-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-N-(2-methylpropyl)methanesulfonamide

Participants

Reaction Conditions

Reaction Steps

A 5-mL vial was charged with N-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-piperazinyl)methyl)-N-(2-methylpropyl)methanesulfonamide (0.170 g, 0.386 mmol), 2-(2-chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol (0.124 g, 0.442 mmol, Intermediate D), DIPEA (0.202 mL, 1.16 mmol), and 1,4-dioxane (2 mL). The vial was sealed and stirred at 100° C. for 21 h. The reaction mixture was allowed to cool to room temperature and partitioned between water (20 mL) and EtOAc (20 mL). The aqueous phase was extracted with EtOAc (20 mL) and the combined organic extracts were washed with saturated aqueous NaCl (40 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (25 g of silica gel, 40 to 100% EtOAc in hexanes followed by 0-10% (2M NH3 in MeOH) in CH2Cl2) to afford N-(((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-N-(2-methylpropyl)methanesulfonamide (0.0454 g) as a brown solid.

Provenance & Evidence