反应详情

温度

60 °C

3-bromo-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-ol (60.0 mg, 0.205 mmol), tert-butyl 3-(bromomethyl)piperidine-1-carboxylate (114 mg, 0.410 mmol), and NaH (29.5 mg, 0.737 mmol) were suspended in DMF (2 ml), then heated to 60° C. After 2 h, the reaction mixture was quenched with 1 ml of saturated aqueous ammonium chloride, diluted in ethyl acetate, washed with saturated aqueous sodium bicarbonate and brine. The combined aqueous layers were extracted with ethyl acetate (1×30 mL), and the combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (methanol/ethyl acetate gradient) afford a yellow oil. The residue was purified by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water+0.05% TFA. The fractions containing product were combined and diluted in ethyl acetate, then washed with aqueous sodium bicarbonate and dried over sodium sulfate, filtered and concentrated to afford tert-butyl 3-({[3-bromo-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-4-yl]oxy}methyl)piperidine-1-carboxylate.

1. customthe reaction mixture was quenched with 1 ml of saturated aqueous ammonium chloride
2. additiondiluted in ethyl acetate
3. washwashed with saturated aqueous sodium bicarbonate and brine
4. extractionThe combined aqueous layers were extracted with ethyl acetate (1×30 mL)
5. dry with materialthe combined organic layers were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified by column chromatography on silica gel (methanol/ethyl acetate gradient)
9. customafford a yellow oil
10. customThe residue was purified by preparative HPLC Reverse phase (C-18)
11. washeluting with Acetonitrile/Water+0.05% TFA
12. additionThe fractions containing product
13. additiondiluted in ethyl acetate
14. washwashed with aqueous sodium bicarbonate
15. dry with materialdried over sodium sulfate
16. filtrationfiltered
17. concentrationconcentrated