反应详情

温度

5 °C

Intermediate (6c), 2-[5-Amino-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester (100 mg, 0.22 mmol) was stirred in dichloromethane (5 mL) at RT with triethylamine (0.092 mL, 0.66 mmol). The reaction mixture was cooled to 5° C. and then a solution of intermediate (6h), 1-((S)-1-Phenyl-ethyl)-1H-pyrazole-4-carbonyl chloride, (54 mg, 0.231 mmol) in dichloromethane (1 mL) was added drop wise. After addition the reaction was stirred at RT for 1 hour and then the reaction mixture was concentrated in vacuo and the residue partitioned between ethyl acetate (10 mL) and aqueous saturated sodium hydrogen carbonate solution (10 mL). The organic layer was separated and the aqueous was extracted with a further portion of ethyl acetate (10 mL). The combined ethyl acetate layers were washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant crude product was purified by flash chromatography on SiO2 eluting with hexane—50% ethyl acetate/hexane (gradient) to afford the desired intermediate, 2-(1-Methyl-2-oxo-5-{[1-((S)-1-phenyl-ethyl)-1H-pyrazole-4-carbonyl]-amino}-1,2-dihydro-pyridin-3-yl)-indole-1-carboxylic acid tert-butyl ester, 0.108 g, 76%.

1. additionAfter addition the reaction
2. concentrationthe reaction mixture was concentrated in vacuo
3. customthe residue partitioned between ethyl acetate (10 mL) and aqueous saturated sodium hydrogen carbonate solution (10 mL)
4. customThe organic layer was separated
5. extractionthe aqueous was extracted with a further portion of ethyl acetate (10 mL)
6. washThe combined ethyl acetate layers were washed with brine
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated in vacuo
9. customThe resultant crude product was purified by flash chromatography on SiO2 eluting with hexane—50% ethyl acetate/hexane (gradient)