反应详情

温度

0 °C

In a round-bottomed flask, 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (412 mg, 0.93 mmol) was suspended in 1,4-dioxane (15 ml) and water (3 ml). The suspension was cooled to 0° C. and sulfamic acid (543 mg, 5.59 mmol) was added. Then, a solution of sodium chlorite (80%, 137 mg, 1.21 mmol) and potassium dihydrogen phosphate (1.52 g, 11.2 mmol) in water (9 ml) was added via dropping funnel over ˜20 min. After the addition was complete, the ice bath was removed and the reaction mixture was stirred at room temperature for 3 h. THF (15 ml) was added and the reaction mixture was stirred at room temperature for an additional 3 h. The reaction mixture 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 ethyl acetate/hexanes to afford 358 mg (84%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid as a light yellow powder.

1. customover ˜20 min
2. additionAfter the addition
3. customthe ice bath was removed
4. additionTHF (15 ml) was added
5. stirringthe reaction mixture was stirred at room temperature for an additional 3 h
6. additionThe reaction mixture was diluted with water
7. extractionextracted with EtOAc (2×)
8. washThe combined organic layers were washed with water and brine
9. dry with materialthen dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was triturated with ethyl acetate/hexanes