反应详情

LiHMDS (1.519 mL, 1.0 M in THF, 1.519 mmol) was 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 (0.220 g, 0.506 mmol) and 5-amino-2-methoxypyridine (0.094 g, 0.759 mmol) in THF (3.00 mL, 36.6 mmol) at 0° C. and the mixture was stirred at the same temperature for 1 h. The reaction mixture was diluted with NH4Cl(aq) and water (10 mL each) and diluted with ethyl acetate (10 mL). The separated aqueous layer was extracted with ethyl acetate (2×10 mL) and the combined organic layers were washed with brine, dried over Na2SO4, concentrated and purified by flash column chromatography (ISCO Combiflash system, Teledyne ISCO, Lincoln, Nebr., hexanes to 50% ethyl acetates in hexanes) to give tert-butyl 4-((6-(6-methoxypyridin-3-ylamino)-5-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)pyridin-3-yl)methyl)piperazine-1-carboxylate (0.133 g, 49%) as a yellow solid. LCMS (API-ES) m/z 538 (M+H)+; 1H NMR (400 MHz, CDCl3) δ 11.42 (s, 1H) 8.81 (br. s., 1H) 8.36 (d, J=2.74 Hz, 1H) 8.27 (br. s., 1H) 8.10 (dd, J=8.71, 2.64 Hz, 1H) 6.79 (d, J=8.80 Hz, 1H) 3.95 (s, 3H) 3.50 (s, 2H) 3.43 (br. s., 4H) 2.67 (s, 3H) 2.66 (br. s., 3H) 2.42 (br. s., 4H) 1.45 (s, 9H).

1. extractionThe separated aqueous layer was extracted with ethyl acetate (2×10 mL)
2. washthe combined organic layers were washed with brine
3. dry with materialdried over Na2SO4
4. concentrationconcentrated
5. custompurified by flash column chromatography (ISCO Combiflash system, Teledyne ISCO, Lincoln, Nebr., hexanes to 50% ethyl acetates in hexanes)