Diisopropylethylamine → 2-(2-(4-((6-Chloro-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol

Participants

Reaction Conditions

Reaction Steps

To a 20 mL vial was added 1-((6-chloro-3-pyridinyl)sulfonyl)-3-(1-propyn-1-yl)piperazine (1.70 g, 7.47 mmol, Example 240, Step 4), diisopropylethylamine (4.20 mL, 24.2 mmol), and NMP (8.0 mL), and 2-(2-chloro-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol (1.4 g, 6.37 mmol, Intermediate E). The vial was sealed and heated at 140° C. for 9 h. The reaction mixture was cooled to rt and partitioned between EtOAc (200 mL) and water (100 mL). The aqueous layer was extracted with EtOAc (2×75 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The crude product was purified by column chromatography (120 g of silica, 10 to 50% EtOAc in hexanes) to afford 2-(2-(4-((6-chloro-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1-trifluoro-2-propanol (1.5 g) as a light yellow solid.

Provenance & Evidence