Acetic Acid → 1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide

HRID 8571Notes

Reaction equation

HRID 8571 reaction equation
[C:1]([C:3]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][CH:10]=2)[N:5]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])[N:4]=1)#[N:2].C[O-].[Na+].[Cl-].[NH4+:24].C(O)(=O)C>CO>[F:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[CH2:12][N:5]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:11]2[C:3]([C:1](=[NH:24])[NH2:2])=[N:4]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 25517Ammonium ChlorideHCID 10942334Sodium MethoxideHCID 114025001-((2-Fluorophenyl)methyl)pyrazolo(3,4-b)pyridine-3-carbonitrile

Product 1

HCID 114039861-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

108.00 g (0.43 mol) of 1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile (example I, step 4) are dissolved in one liter of methanol and added dropwise to a solution of 94.73 g (1.67 mol; purity: 95%) of sodium methoxide in 3 l of methanol. After stirring at RT for 2 hours, 28.83 g (0.54 mol) of ammonium chloride are added, and subsequently 100.03 g (1.67 mol) of glacial acetic acid are added dropwise. This solution is stirred under reflux overnight. The solvent is removed in vacuo, the residue is twice suspended in acetone and the insoluble solid is filtered off with suction. The latter is dissolved in 1.5 l of ethyl acetate, and 590 ml of an aqueous 20% strength sodium carbonate solution are added. Stirring for 20 minutes is followed by dilution with 200 ml of 1N sodium hydroxide solution. The organic phase is washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered. The solvent is removed in vacuo. 99.10 g (86% of theory) of the product are obtained.

Workup

  1. stirringThis solution is stirred
  2. temperatureunder reflux overnight
  3. customThe solvent is removed in vacuo
  4. filtrationthe insoluble solid is filtered off with suction
  5. dissolutionThe latter is dissolved in 1.5 l of ethyl acetate
  6. addition590 ml of an aqueous 20% strength sodium carbonate solution are added
  7. stirringStirring for 20 minutes
  8. washThe organic phase is washed with saturated aqueous sodium chloride solution
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. customThe solvent is removed in vacuo
  12. custom99.10 g (86% of theory) of the product are obtained

Sources & evidence

ORD record
ord-2089e7109b4c498594f3f7ea1206c5d4
Source dataset
uspto-grants-2006_08
Patent number
US07091198B1

Reaction notes

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