Acetic Acid → 1-(2-Fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboximidamide

HRID 536487Notes

Reaction equation

HRID 536487 reaction equation
[F:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[CH2:4][N:5]1[C:9]2[CH2:10][CH2:11][CH2:12][C:8]=2[C:7]([C:13]#[N:14])=[N:6]1.C[O-].[Na+].C(O)(=O)C.[Cl-].[NH4+:27]>CO>[F:1][C:2]1[CH:18]=[CH:17][CH:16]=[CH:15][C:3]=1[CH2:4][N:5]1[C:9]2[CH2:10][CH2:11][CH2:12][C:8]=2[C:7]([C:13](=[NH:27])[NH2:14])=[N:6]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 25517Ammonium ChlorideHCID 10942334Sodium MethoxideHCID 712853771-(2-Fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carbonitrile

Product 1

HCID 866920921-(2-Fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboximidamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Under nitrogen atmosphere, 3.600 g (14.92 mmol) of 1-(2-fluorobenzyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carbonitrile was dissolved in 37 ml of absolute methanol. 1.306 g (24.17 mmol) of sodium methylate was added and it was stirred for 4 h at RT. 1.452 g (24.17 mmol) of acetic acid and 1.197 g (22.38 mmol) of ammonium chloride were added and the suspension was stirred overnight at 50° C. The reaction mixture was concentrated by evaporation and the residue was suspended in 100 ml water and 25 ml 1N hydrochloric acid. The mixture was extracted with dichloromethane. The aqueous phase was made basic (pH=12) with 2N sodium hydroxide solution and extracted three times with a mixture of dichloromethane/methanol (v/v=8:2). The combined organic phases were dried over sodium sulphate, concentrated by evaporation, toluene was added and again evaporated to dryness. 1.94 g (50% of theor.) of the target compound was obtained.

Workup

  1. stirringthe suspension was stirred overnight at 50° C
  2. concentrationThe reaction mixture was concentrated by evaporation
  3. extractionThe mixture was extracted with dichloromethane
  4. extractionextracted three times
  5. additionwith a mixture of dichloromethane/methanol (v/v=8:2)
  6. dry with materialThe combined organic phases were dried over sodium sulphate
  7. concentrationconcentrated by evaporation, toluene
  8. additionwas added
  9. customagain evaporated to dryness
  10. custom1.94 g (50% of theor.) of the target compound was obtained

Sources & evidence

ORD record
ord-f283436204bf48b48dc611b8cc215d91
Source dataset
uspto-grants-2014_10
Patent number
US08859569B2

Reaction notes

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