Sodium Hydroxide → 6-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

HRID 1854032Notes

Reaction equation

HRID 1854032 reaction equation
[OH-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]([C:18]([O:20]CC)=O)[C:7]2[CH:12]=[N:11][N:10]([CH:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:8]=2[N:9]=1.[NH2:23][CH2:24][C:25]1[C:26](=[O:33])[NH:27][C:28]([CH3:32])=[CH:29][C:30]=1[CH3:31].C1CN([P+]([O:50]N2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CCO.CCOC(C)=O.O>[Br:3][C:4]1[CH:5]=[C:6]([C:18]([NH:23][CH2:24][C:25]2[C:26](=[O:33])[NH:27][C:28]([CH3:32])=[CH:29][C:30]=2[CH3:31])=[O:20])[C:7]2[CH:12]=[N:11][N:10]([CH:13]3[CH2:14][CH2:15][O:50][CH2:16][CH2:17]3)[C:8]=2[N:9]=1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 2724699PyBOPHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 86703404HCID 86703404, compound

Product 1

HCID 867034166-bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Aqueous NaOH (5 equivalent) was added to a solution of ethyl 6-bromo-1-cyclopentyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate (1 equivalent) in EtOH (10 times by volume) and stirred at 60° C. for 1 h. After completion of the reaction, ethanol was removed under reduced pressure and it was acidified using 10% citric acid solution. Extraction was carried out using EtOAc; the combined organic layers were washed with water, brine and dried over anhydrous Na2SO4; filtered and concentrated under reduced pressure. The residue was then dissolved in DMSO (10 times by volume) and 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one (2 equivalents) was added to it. The reaction mixture was stirred at room temperature for 15 min before PYBOP (1.5 equivalents) was added to it and stirring was continued for 5 to 16 h. After completion of the reaction, water was added to it and extraction was carried out using EtOAc. The combined organic layers were washed with water; brine; dried over anhydrous Na2SO4; filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography followed by ether wash to provide the desired intermediate.

Workup

  1. customwas removed under reduced pressure and it
  2. extractionExtraction
  3. washthe combined organic layers were washed with water, brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was then dissolved in DMSO (10 times by volume)
  8. additionwas added to it
  9. stirringstirring
  10. waitwas continued for 5 to 16 h
  11. additionwas added to it and extraction
  12. washThe combined organic layers were washed with water
  13. dry with materialdried over anhydrous Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified by silica gel column chromatography
  17. washwash

Sources & evidence

ORD record
ord-0b2caee7023647d0a5a5124aae6a4e3c
Source dataset
uspto-grants-2015_02
Patent number
US08962620B2

Reaction notes

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