反应详情

LiHMDS, 1.0 M in THF (0.754 mL, 0.754 mmol) was added dropwise to a stirred solution of 2-(2-fluoro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-4-methyl-6-(methylthio)-1,3,5-triazine (0.311 g, 0.754 mmol) (Example 34, Step 5) and 3-amino-6-methoxypyridine (0.094 g, 0.754 mmol) in tetrahydrofuran (10 mL, 0.754 mmol) at −10° 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 (20 mL). The separated aqueous layer was extracted with ethyl acetate (2×20 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., DCM to 5% MeOH in DCM) to give N-(6-methoxypyridin-3-yl)-3-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-amine (237 mg, 0.459 mmol, 60.8% yield) as a yellow solid.

1. extractionThe separated aqueous layer was extracted with ethyl acetate (2×20 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., DCM to 5% MeOH in DCM)