反应详情

To a slightly cooled stirred solution of (R)-tert-butyl 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-yl)methyl)-3-methylpiperazine-1-carboxylate (1.01 g, 1.535 mmol) in DCM (5.0 mL, 78 mmol) was added slowly TFA (4.00 mL, 51.9 mmol) and the mixture was stirred at room temperature for 1 h. The mixture was concentrated and the sticky residue was taken up in a solution of DCM (10.0 mL) to which TEA (2.140 mL, 15.35 mmol) and methanesulfonyl chloride (0.598 mL, 7.68 mmol) was slowly added subsequently at 0° C. The mixture was stirred at the same temperature for 1 h, concentrated, and 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 a crude residue which was purified by flash column chromatography (ISCO Combiflash system, 10% ethyl acetate/hexanes to 70% ethyl acetates in hexanes) to obtain the desired product (R)-4-(2-fluoro-5-((2-methyl-4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.4779 g, 0.752 mmol, 49.0% yield) as a pale yellow foam. m/z (ESI, +ve ion) 636 (M+H)+.

1. temperatureTo a slightly cooled
2. concentrationThe mixture was concentrated
3. additionwas slowly added subsequently at 0° C
4. stirringThe mixture was stirred at the same temperature for 1 h
5. concentrationconcentrated
6. customthe crude product was partitioned between 1 N NaOH(aq) and DCM (20 mL each)
7. extractionThe separated aqueous layer was extracted with DCM (2×20 mL)
8. washthe combined organic layers were washed with brine
9. dry with materialdried over Na2SO4
10. concentrationconcentrated
11. customto give a crude residue which
12. customwas purified by flash column chromatography (ISCO Combiflash system, 10% ethyl acetate/hexanes to 70% ethyl acetates in hexanes)