反应详情

To a solution of 4-(2-fluoro-4-iodophenylamino)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (737 mg, 1.4 mmol), HOBt (231 mg, 1.7 mmol), and EDCI (327 mg, 1.7 mmol) in DMF (15 mL) was added a solution of 2-aminooxy-2-methyl-propan-1-ol hydrochloride (280 mg, 2.0 mmol), and DIPEA (603 μL, 3.6 mmol) in DMF (5 mL). The reaction mixture was stirred at room temperature for 3 days then diluted with water (30 mL) and the aqueous layer extracted with dichloromethane (3×20 mL). The combined organic fractions were filtered through a hydrophobic frit and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—SPE, gradient 0-100% ethyl acetate in cyclohexane) to yield the title compound as a yellow solid (420 mg, 49%). LCMS (Method B): RT=3.47 min, [M+H]+=606.

1. extractionthe aqueous layer extracted with dichloromethane (3×20 mL)
2. filtrationThe combined organic fractions were filtered through a hydrophobic frit
3. concentrationconcentrated in vacuo