Sodium Hydroxide → HCID 68350667, compound

HRID 1854020Notes

Reaction equation

HRID 1854020 reaction equation
[OH-].[Na+].[CH:3]([N:6]1[C:10]2[N:11]=[C:12]([O:20][CH:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)[CH:13]=[C:14]([C:15](OCC)=[O:16])[C:9]=2[CH:8]=[N:7]1)([CH3:5])[CH3:4].[NH2:28][CH2:29][C:30]1[C:31](=[O:38])[NH:32][C:33]([CH3:37])=[CH:34][C:35]=1[CH3:36].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CCO>[CH3:36][C:35]1[CH:34]=[C:33]([CH3:37])[NH:32][C:31](=[O:38])[C:30]=1[CH2:29][NH:28][C:15]([C:14]1[C:9]2[CH:8]=[N:7][N:6]([CH:3]([CH3:4])[CH3:5])[C:10]=2[N:11]=[C:12]([O:20][CH:21]2[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]2)[CH:13]=1)=[O:16]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 2724699PyBOPHCID 70638443-(Aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-oneHCID 68294766HCID 68294766, compound

Product 1

HCID 68350667HCID 68350667, compoundYield 2.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
60 °C

Procedure

Aqueous NaOH (2 equivalent) was added to a solution of ethyl 1-isopropyl-6-((1-methylpiperidin-4-yl)oxy)-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 citric acid solution. Extraction was carried out using DCM; 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, reaction mass was poured into ice water to obtain a solid which was filtered and washed with acetonitrile to provide the desired product (2.5% yield). LCMS: 453.20 (M+1)+; HPLC: 96.37% (@ 254 nm) (Rt; 4.742); 1H NMR (CD3OD, 400 MHz) δ 8.16 (s, 1H), 7.21-7.11 (m, 2H), 7.00 (s, 1H), 6.13 (s, 1H), 5.16-5.11 (m, 1H), 4.53 (d, 2H, J=5.2 Hz), 3.65 (d, 1H, J=13.2 Hz), 3.48-3.45 (m, 2H), 3.38-3.31 (m, 2H), 2.94 (s, 3H), 2.53 (d, 1H, J=12 Hz), 2.41 (s, 3H), 2.40 (m, 1H), 2.25 (s, 3H), 2.20-2.13 (m, 1H), 2.02-1.95 (1H), 1.54 (d, 6H, J=6.8 Hz).

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. customAfter completion of the reaction, reaction mass
  12. customto obtain a solid which
  13. filtrationwas filtered
  14. washwashed with acetonitrile

Sources & evidence

ORD record
ord-579631f8776543869d20c566de6c3346
Source dataset
uspto-grants-2015_02
Patent number
US08962620B2

Reaction notes

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