反应详情

温度

105 °C

3-Methyl-1-(1-methylethyl)-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid (1.5 g, 6.38 mmol) was added to a solution of THF (15 mL) followed by addition of phosphorous oxychloride (8.9 mL, 96 mmol), and the contents heated at 105° C. overnight. After cooling to room temperature, the contents were concentrated in vacuo to remove most of the volatiles. The residual contents were slowly poured into a solution of iced water and 1N NaOH (10 mL), and the contents were stirred at room temperature for 24 h, during which time solid precipitation ensued. Additional 1N NaOH was added, upon which the solids went into solution. After stirring at room temperature for an additional 30 min., the contents were cooled in an ice bath and the mixture slowly acidified to pH=3-4 by slow addition of 6N HCl, to afford a heterogenous mixture. The mixture was filtered and a white solid set aside. The aq. layer was further extracted with EtOAc and DCM. The combined organic layers dried were dried over MgSO4, filtered and concentrated in vacuo. The resultant light brown solid was triturated in EtOAc/EtOH (1:1) and filtered to afford a first crop of white solid product, which was set aside. The filtrate was again concentrated in vacuo. The residue was diluted with EtOAc, sonicated, treated with hexanes, and filtered. The process was repeated. The isolated solid product crops were dried under vacuum (3 h) and collected as 1.33 g (80%). LCMS E-S (M+H): 254.3 1H NMR (400 MHz, DMSO-d6) δ ppm 1.46 (d, 6 H), 2.60 (s, 3 H), 5.10 (quin, J=6.63 Hz, 1 H), 7.50 (s, 1 H), 14.17 (br. s., 1 H).

1. temperatureAfter cooling to room temperature
2. concentrationthe contents were concentrated in vacuo
3. customto remove most of the volatiles
4. additionThe residual contents were slowly poured into a solution of iced water and 1N NaOH (10 mL)
5. additionAdditional 1N NaOH was added, upon which the solids
6. stirringAfter stirring at room temperature for an additional 30 min.
7. temperaturethe contents were cooled in an ice bath
8. additionthe mixture slowly acidified to pH=3-4 by slow addition of 6N HCl
9. customto afford a heterogenous mixture
10. filtrationThe mixture was filtered
11. extractionThe aq. layer was further extracted with EtOAc and DCM
12. customThe combined organic layers dried
13. dry with materialwere dried over MgSO4
14. filtrationfiltered
15. concentrationconcentrated in vacuo
16. customThe resultant light brown solid was triturated in EtOAc/EtOH (1:1)
17. filtrationfiltered
18. customto afford a first crop of white solid product, which
19. concentrationThe filtrate was again concentrated in vacuo
20. additionThe residue was diluted with EtOAc
21. customsonicated
22. additiontreated with hexanes
23. filtrationfiltered
24. customThe isolated solid product crops were dried under vacuum (3 h)
25. customcollected as 1.33 g (80%)