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

HRID 2203373Notes

Reaction equation

HRID 2203373 reaction equation
[F:1][C:2]([F:17])([F:16])[CH2:3][CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]#[N:15])=[N:6]1.C[O-].[Na+].C(O)(=O)C.[Cl-].[NH4+:26]>CO>[F:17][C:2]([F:1])([F:16])[CH2:3][CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14](=[NH:26])[NH2:15])=[N:6]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 25517Ammonium ChlorideHCID 10942334Sodium MethoxideHCID 866790091-(3,3,3-trifluoropropyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile

Product 1

HCID 866790101-(3,3,3-trifluoropropyl)-1H-pyrazolo[3,4-b]pyridine-3-carboximidamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

To the intermediate from Step A above (44.4 g, 185 mmol) in MeOH (16 mL) at rt was added sodium methoxide (13.98 g, 259 mmol). After stirring for 3 hours, acetic acid (42.3 mL, 739 mmol) and ammonium chloride (12.85 g, 240 mmol) were added to the reaction. The resulting slurry was heated to 65° C. and stirred for 4 hours. The reaction was then cooled to rt and quenched with EtOAc and saturated aqueous NaHCO3. The aqueous layer was removed and back extracted with EtOAc (4×). The combined organic layers were washed with 20% brine and dried over Na2SO4, filtered and the solvent removed under vacuum. EtOAc was added and the precipitated product was filtered and washed with methyl tert-butyl ether. The solid was dried at rt under vacuum oven overnight and the material used without further purification. 1H NMR (500 MHz, CH3OH-d4): δ 8.74 (d, J=4.57 Hz, 1H); 8.52 (d, J=8.32 Hz, 1H); 7.51 (dd, J=8.31, 4.44 Hz, 1H); 4.96 (t, J=6.91 Hz, 3H); 3.08-2.97 (m, 2H). m/z=258.3 (M+H).

Workup

  1. stirringstirred for 4 hours
  2. temperatureThe reaction was then cooled to rt
  3. customquenched with EtOAc and saturated aqueous NaHCO3
  4. customThe aqueous layer was removed
  5. extractionback extracted with EtOAc (4×)
  6. washThe combined organic layers were washed with 20% brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customthe solvent removed under vacuum
  10. additionEtOAc was added
  11. filtrationthe precipitated product was filtered
  12. washwashed with methyl tert-butyl ether
  13. customThe solid was dried at rt under vacuum oven overnight
  14. customthe material used without further purification

Sources & evidence

ORD record
ord-0e30519d8cbd41bbb9937445315ff81e
Source dataset
uspto-grants-2016_06
Patent number
US09365574B2

Reaction notes

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