Trifluoroacetic acid → HCID 68767958, compound

Temperature

-78 °C

1.7M t-BuLi in heptane (1.23 mL, 2.09 mmol) was added to a solution of tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (0.50 g, 1.00 mmol) in THF (5 mL) at −78° C. The reaction was stirred at −78° C. for 30 minutes, and cyclobutanone (0.23 mL, 2.99 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. Saturated NH4Cl (10 mL) was added, extracted with ethyl acetate (30 mL), washed with brine, dried (sodium sulfate) and concentrated in vacuo. The residue was suspended in triethylsilane (2.31 g, 19.9 mmol), and TFA (2 mL) was added. After 1 hour, the solvent was removed, and the residue was dissolved in TFA (5 mL) and heated at 68° C. for 5 hours. The solvent was removed. The residue was dissolved in DCM (10 mL) and Boc2O (0.434 g, 1.99 mmol) was added. The reaction was stirred at room temperature for 1 hour. The solvent was removed. The residue was dissolved in THF (5 mL) and 2N LiOH in water (5 mL) was added. It was stirred at room temperature for 2 hours. Ethyl acetate (50 mL) was added. The organic layer was separated, washed with brine, dried (sodium sulfate) and concentrated in vacuo. The residue obtained was purified by flash chromatography on silica gel (hexane:ethyl acetate=1:1) to give a solid. It was dissolved in EtOH (10 mL), and 10% Pd/C (0.11 g, 0.10 mmol) was added. The mixture was charged with 50 psi hydrogen and shaken for 6 hours. The catalyst was removed by filtration and concentrated in vacuo. The residue obtained was purified by flash chromatography (hexane:ethyl acetate=1:1) to give tert-butyl 4-(5-cyclobutyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (0.14 g, 39%) as a solid. LCMS (APCI+) m/z 358(M+H)+.

1. temperatureto warm to room temperature
2. stirringstirred for 1 hour
3. extractionextracted with ethyl acetate (30 mL)
4. washwashed with brine
5. dry with materialdried (sodium sulfate)
6. concentrationconcentrated in vacuo
7. waitAfter 1 hour
8. customthe solvent was removed
9. dissolutionthe residue was dissolved in TFA (5 mL)
10. temperatureheated at 68° C. for 5 hours
11. customThe solvent was removed
12. dissolutionThe residue was dissolved in DCM (10 mL)
13. stirringThe reaction was stirred at room temperature for 1 hour
14. customThe solvent was removed
15. dissolutionThe residue was dissolved in THF (5 mL)
16. addition2N LiOH in water (5 mL) was added
17. stirringIt was stirred at room temperature for 2 hours
18. additionEthyl acetate (50 mL) was added
19. customThe organic layer was separated
20. washwashed with brine
21. dry with materialdried (sodium sulfate)
22. concentrationconcentrated in vacuo
23. customThe residue obtained
24. customwas purified by flash chromatography on silica gel (hexane:ethyl acetate=1:1)
25. customto give a solid
26. stirringshaken for 6 hours
27. customThe catalyst was removed by filtration
28. concentrationconcentrated in vacuo
29. customThe residue obtained
30. customwas purified by flash chromatography (hexane:ethyl acetate=1:1)

ORD record

ord-9e1a7f1ff8044a9ca67973d8775154eb

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08372842B2