反应详情

温度

0 °C

In a 50 ml round-bottomed flask, 4-{6-fluoro-3-[7-formyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (190 mg, 0.32 mmol) was dissolved in THF (7 ml) and water (1.4 ml). The light yellow solution was cooled to 0° C. and sulfamic acid (186 mg, 1.92 mmol) was added. Then, a solution of sodium chlorite (80%, 50 mg, 0.44 mmol) and potassium dihydrogen phosphate (522 mg, 3.83 mmol) in water (4.2 ml) was added dropwise via pipette. After the addition was complete, the ice bath was removed and the reaction mixture was stirred at room temperature for 1.5 h. The reaction was diluted with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was triturated with hexanes to afford 176 mg (90%) of 2-[1-(1-tertbutoxycarbonyl-piperidin-4-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid as a light yellow powder.

1. additionAfter the addition
2. customthe ice bath was removed
3. additionThe reaction was diluted with water
4. extractionextracted with EtOAc (2×)
5. washThe combined organic layers were washed with water and brine
6. dry with materialthen dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was triturated with hexanes