反应详情

TFA (4.00 mL, 51.9 mmol) was slowly added to a slightly cooled stirred solution of tert-butyl 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)pyridin-3-yl)methyl)piperidine-1-carboxylate (0.2611 g, 0.350 mmol) in DCM (5.00 mL, 78 mmol) and the mixture was stirred at room temperature for 1 h. The mixture was concentrated (under vacuum to remove as much TFA as possible). The sticky residue was taken up in DCM (10.00 mL) and TEA (0.487 mL, 3.50 mmol) followed by methanesulfonyl chloride (0.082 mL, 1.049 mmol) were slowly added at 0° C. The mixture was stirred for 1 h and then concentrated. The crude product was partitioned between 1 N NaOH(aq) and DCM (20 mL each). The separated aqueous layer was extracted with DCM (2×20 mL) and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated to give the crude residue which was purified with flash column chromatography (ISCO Combiflash system, 10% to 50% ethyl acetate in hexanes) to give the desired product N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-((1-(methylsulfonyl)piperidin-4-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.1923 g, 0.265 mmol, 76% yield) as a yellow film. m/z (ESI, +ve ion) 725.2 (M+H)+.

1. temperaturea slightly cooled
2. concentrationThe mixture was concentrated
3. custom(under vacuum to remove as much TFA as possible)
4. additionwere slowly added at 0° C
5. stirringThe mixture was stirred for 1 h
6. concentrationconcentrated
7. customThe crude product was partitioned between 1 N NaOH(aq) and DCM (20 mL each)
8. extractionThe separated aqueous layer was extracted with DCM (2×20 mL)
9. washthe combined organic layers were washed with brine
10. dry with materialdried over Na2SO4
11. concentrationconcentrated
12. customto give the crude residue which
13. customwas purified with flash column chromatography (ISCO Combiflash system, 10% to 50% ethyl acetate in hexanes)