Dichloromethane → 5-Amino-1-(2-chloro-4-fluorophenyl)-1H-pyrazole-4-carbonitrile

HRID 1098113Notes

Reaction equation

HRID 1098113 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[NH:10][NH2:11].C(Cl)Cl.[OH-].[Na+].C(O[CH:20]=[C:21]([C:24]#[N:25])[C:22]#[N:23])C>CO>[NH2:25][C:24]1[N:10]([C:4]2[CH:5]=[CH:6][C:7]([F:9])=[CH:8][C:3]=2[Cl:2])[N:11]=[CH:20][C:21]=1[C:22]#[N:23]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 671522-(Ethoxymethylene)propanedinitrileHCID 247210492-Chloro-4-fluorophenylhydrazine hydrochloride

Product 1

HCID 575045995-Amino-1-(2-chloro-4-fluorophenyl)-1H-pyrazole-4-carbonitrileYield 96.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

2-Chloro-4-fluorophenyl hydrazine hydrochloride (CAS 497959-29-2) (25.0 g, 126.9 mmol) was partitioned between DCM (250 mL) and 2M NaOH (100 mL). The organic phase was separated and washed sequentially with water (2×150 mL) and brine (150 mL), dried over MgSO4 and evaporated to give the free base. This oil was dissolved in MeOH (200 mL) under nitrogen at −5° C. and 2-(ethoxymethylene)malononitrile (15.5 g, 127 mmol) was added portionwise. The resulting mixture was stirred at 0° C. for 2 hours then at reflux for a further 2 hours. After cooling, the mixture was evaporated to provide 5-amino-1-(2-chloro-4-fluorophenyl)-1H-pyrazole-4-carbonitrile (28.9 g).

Workup

  1. customThe organic phase was separated
  2. washwashed sequentially with water (2×150 mL) and brine (150 mL)
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customto give the free base
  6. temperatureat reflux for a further 2 hours
  7. temperatureAfter cooling
  8. customthe mixture was evaporated

Sources & evidence

ORD record
ord-57015418acba4b4a88d38cdee3c3aad0
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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