Dichloromethane → 2-(2-Fluoro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-4-methyl-6-(methylthio)-1,3,5-triazine

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Reaction Steps

TFA (4.00 mL, 51.9 mmol) was slowly added to a stirred solution of tert-butyl 4-((6-fluoro-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyridin-3-yl)methyl)piperazine-1-carboxylate (0.853 g, 1.963 mmol) in DCM (5.00 mL, 78 mmol) cooled in an ice bath, and the mixture was then stirred at room temperature for 1 h. The mixture was concentrated, and the sticky residue was dissolved in DCM (10 mL) and cooled in an ice bath, and triethylamine (1.368 mL, 9.82 mmol) was added. Methanesulfonyl chloride (0.459 mL, 5.89 mmol) was slowly added to the mixture, which was then stirred at the same temperature for 1 h, concentrated, and the residue was adsorbed onto a plug of silica gel and chromatographed through a RediSep®, Teledyne ISCO, Lincoln, Nebr., pre-packed silica gel column (pure DCM to 10% MeOH in DCM) to give a solid which was washed with IPA to give 2-(2-fluoro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-4-methyl-6-(methylthio)-1,3,5-triazine (0.64 g, 79%) as a white solid. LCMS (API-ES) m/z 413 (M+H)+; 1H NMR (400 MHz, d6-DMSO) δ 8.58 (dd, J=9.29, 2.25 Hz, 1H) 8.37 (s, 1H) 3.67 (s, 2H) 3.01-3.19 (m, 4H) 2.87 (s, 3H) 2.61 (s, 3H) 2.60 (s, 3H) 2.47-2.49 (m, 4H).

Provenance & Evidence