Sodium Carbonate → Tert-butyl 4-((6-fluoro-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyridin-3-yl)methyl)piperazine-1-carboxylate

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Reaction Conditions

Reaction Steps

1,4-dioxane (15 mL) and H2O (3.00 mL) were added to a mixture of 2-chloro-4-methyl-6-(methylthio)-1,3,5-triazine (0.560 g, 3.19 mmol), 5-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)-2-fluoropyridin-3-ylboronic acid (1.03 g, 3.04 mmol), Na2CO3 (0.805 g, 7.59 mmol), and Pd(Ph3P)4 (0.175 g, 0.152 mmol) and the stirred suspension was heated at 80° C. overnight. After cooling, the mixture was passed a short plug of Na2SO4, washed with EtOAc (×2) and concentrated. The residue was adsorbed onto a plug of silica gel and chromatographed through a RediSep®, Teledyne ISCO, Lincoln, Nebr., pre-packed silica gel column (hexanes to 30% ethyl acetate in hexanes) to give tert-butyl 4-((6-fluoro-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyridin-3-yl)methyl)piperazine-1-carboxylate (0.9676 g, 74%) as a white solid. LCMS (API-ES) m/z 435 (M+H)+; 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J=9.00 Hz, 1H) 8.30 (s, 1H) 3.58 (s, 2H) 3.44 (br. s., 4H) 2.66 (s, 3H) 2.64 (s, 3H) 2.43 (d, J=4.50 Hz, 4H) 1.46 (s, 9H).

Provenance & Evidence