反应详情

温度

40 °C

To a solution of intermediate (1c), 2-[5-carboxy-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]indole-1-carboxylic acid tert-butyl ester, (3 g, 6.2 mmol) in tetrahydrofuran (100 mL) was added intermediate (2H), 1H-pyrazol-4-ylamine (0.62 g, 7.46 mmol), 1-hydroxybenzotriazole hydrate (1.09 g, 8.07 mmol), N,N-diisopropylethylamine (2.4 g, 3.24 mL, 18.6 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.55 g, 8.07 mmol). The reaction mixture was heated at 40° C. for 2 hours. The reaction mixture was cooled and partitioned between ethyl acetate and aqueous saturated sodium hydrogen bicarbonate solution. The ethyl acetate layer was separated and washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant crude product was purified by flash chromatography on SiO2 eluting with hexane—66% ethyl acetate/hexane (gradient) to afford the desired title compound as a yellow solid, 1.36 g, 40%.

1. temperatureThe reaction mixture was cooled
2. custompartitioned between ethyl acetate and aqueous saturated sodium hydrogen bicarbonate solution
3. customThe ethyl acetate layer was separated
4. washwashed with brine
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated in vacuo
7. customThe resultant crude product was purified by flash chromatography on SiO2 eluting with hexane—66% ethyl acetate/hexane (gradient)