反应详情

Lithium 2-(2-(2-(2-((4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate (I7) (0.130 g, 0.220 mmol) was dissolved in dry THF (7 mL) and dry DMF (1 mL) under an atmosphere of nitrogen. To the solution were added 1-hydroxybenzotriazole (0.036 g, 0.26 mmol) and EDCI (0.051 g, 0.26 mmol) and N,N-diisopropylethylamine (0.153 mL, 0.879 mmol) and the reaction mixture was stirred at room temperature for 10 minutes. Methylamine hydrochloride (0.059 g, 0.88 mmol) was added in one portion, and the reaction was stirred at room temperature for 60 hours. The volatiles were removed in vacuo and the residual solution was diluted with EtOAc (100 mL) and sat. aq. NaHCO3 (80 mL). The layers were separated and the aqueous layer was extracted with EtOAc (70 mL), the organic layers were combined and washed with water (100 mL), brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo to give a pale yellow solid. The crude product was purified by silica gel chromatography (Biotage Isolera, 40 g Si Cartridge, 0-100% EtOAc in petroleum benzine 40-60° C., then 0-60% methanol in EtOAc) to give the title compound (I56) (0.091 g, 69% yield) as a pale yellow solid;

1. stirringthe reaction was stirred at room temperature for 60 hours
2. customThe volatiles were removed in vacuo
3. additionthe residual solution was diluted with EtOAc (100 mL) and sat. aq. NaHCO3 (80 mL)
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with EtOAc (70 mL)
6. washwashed with water (100 mL), brine (100 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customto give a pale yellow solid
11. customThe crude product was purified by silica gel chromatography (Biotage Isolera, 40 g Si Cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.