反应详情

A solution of 4-({2-[4-(2,5-dioxopyrrolidin-1-yl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethyl}amino)-4-oxobutanoic acid (3.16 g, 6.39 mmol) in dichloromethane (100 mL) was treated with triethylamine (2.67 mL, 19.2 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.67 g, 19.2 mmol), tert-butylcarbazate (2.46 g, 19.2 mmol) and N,N-dimethylpyridin-4-amine (78 mg, 0.64 mmol). The reaction mixture was stirred for 4 days and then was treated with 100 mL of water. The layers were separated and the aqueous portion was extracted with chloroform (50 mL). The combined organic layers were washed successively with water (50 mL) and brine (50 mL). The organic portion was dried over sodium sulfate, filtered, and concentrated under reduced pressure to give a white foam. The white foam was dissolved in dichloromethane (50 mL) and treated with ethylene diamine (1 mL). After stirring for 4 hours, the reaction mixture was treated with water (50 mL) and chloroform (50 mL) and the layers were separated. The aqueous portion was extracted with chloroform (2×25 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL). The organic layer was concentrated and purification of the crude product by chromatography on silica gel (gradient elution, 25%-100% CMA in chloroform) followed by crystallization from dichloromethane gave 1.67 g of tert-butyl 2-[4-({2-[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethyl}amino)-4-oxobutanoyl]hydrazinecarboxylate as a white powder.

1. customThe layers were separated
2. extractionthe aqueous portion was extracted with chloroform (50 mL)
3. washThe combined organic layers were washed successively with water (50 mL) and brine (50 mL)
4. dry with materialThe organic portion was dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customto give a white foam
8. stirringAfter stirring for 4 hours
9. customthe layers were separated
10. extractionThe aqueous portion was extracted with chloroform (2×25 mL)
11. washThe combined organic layers were washed with water (50 mL) and brine (50 mL)
12. concentrationThe organic layer was concentrated
13. custompurification of the crude product by chromatography on silica gel (gradient elution, 25%-100% CMA in chloroform)
14. customfollowed by crystallization from dichloromethane