Acetic Acid → 1-(2,3-Difluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboximidamide

HRID 570533Notes

Reaction equation

HRID 570533 reaction equation
C[O-].[Na+].[F:4][C:5]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:6]=1[CH2:7][N:8]1[C:12]2=[N:13][C:14]([CH3:17])=[N:15][CH:16]=[C:11]2[C:10]([C:18]#[N:19])=[N:9]1.[Cl-].[NH4+:26].C(O)(=O)C>CO>[F:4][C:5]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:6]=1[CH2:7][N:8]1[C:12]2=[N:13][C:14]([CH3:17])=[N:15][CH:16]=[C:11]2[C:10]([C:18](=[NH:26])[NH2:19])=[N:9]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 25517Ammonium ChlorideHCID 10942334Sodium MethoxideHCID 866920991-(2,3-Difluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carbonitrile

Product 1

HCID 866921001-(2,3-Difluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboximidamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Under an argon atmosphere, 0.73 ml (3.35 mmol) of a 25% sodium methoxide solution was initially charged in methanol, and 1.040 g (purity 92%, 3.35 mmol) of 1-(2,3-difluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carbonitrile dissolved in 4 ml of absolute methanol were added. The mixture was stirred at RT for 1 h. Subsequently, 215 mg (4.03 mmol) of ammonium chloride and 786 mg (13.08 mmol) of acetic acid were added and the mixture was heated to reflux for 2 h. The reaction mixture was concentrated, and the residue was admixed with 10 ml of ethyl acetate and 15 ml of water and basified (pH=10) with 2N sodium hydroxide solution. The mixture was stirred at RT for 1 h, water was added and the mixture was extracted with ethyl acetate. The organic phase was dried over sodium sulphate, concentrated and dried under high vacuum. 840 mg (purity 85%, 70% of theory) of the target compound were obtained.

Workup

  1. additionwere added
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 2 h
  4. concentrationThe reaction mixture was concentrated
  5. stirringThe mixture was stirred at RT for 1 h
  6. additionwater was added
  7. extractionthe mixture was extracted with ethyl acetate
  8. dry with materialThe organic phase was dried over sodium sulphate
  9. concentrationconcentrated
  10. customdried under high vacuum
  11. custom840 mg (purity 85%, 70% of theory) of the target compound were obtained

Sources & evidence

ORD record
ord-6f210720d69a4c829d7d02547862d6f8
Source dataset
uspto-grants-2015_05
Patent number
US09023849B2

Reaction notes

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