反应详情

3-(2-Fluoro-4-iodo-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid sodium salt (0.20 g, 0.46 mmol), O—[(S)-2-(tert-butyldimethylsilanyloxy)-propyl]-hydroxylamine (95 mg, 0.46 mmol), HOBT (69 mg, 0.51 mmol), EDCI (97 mg, 0.51 mmol) and DIPEA (0.08 ml, 0.46 mmol) were suspended in a mixture of THF (3 ml) and DMF (1 ml). The reaction was stirred at room temperature for 16 hours. The reaction mixture was concentrated in vacuo and the residue dissolved in ethyl acetate (20 ml) and washed with aqueous saturated sodium bicarbonate solution (20 ml). The aqueous layer was isolated and extracted with ethyl acetate (2×10 ml) and the combined organic layers dried, washed with brine and dried over magnesium sulfate before concentrating in vacuo. The crude residue was purified by flash chromatography (SiO2, gradient 1-3% methanol in dichloromethane) to yield the title compound as an off-white solid (171 mg, 62%). LCMS (method B): RT=3.00 min, M+H+=599.

1. concentrationThe reaction mixture was concentrated in vacuo
2. dissolutionthe residue dissolved in ethyl acetate (20 ml)
3. washwashed with aqueous saturated sodium bicarbonate solution (20 ml)
4. customThe aqueous layer was isolated
5. extractionextracted with ethyl acetate (2×10 ml)
6. customthe combined organic layers dried
7. washwashed with brine
8. dry with materialdried over magnesium sulfate
9. concentrationbefore concentrating in vacuo
10. customThe crude residue was purified by flash chromatography (SiO2, gradient 1-3% methanol in dichloromethane)