Triethylamine → 5-Amino-1-(2,6-dichlorophenyl)-3-isopropyl-1H-pyrazole-4-carbonitrile

HRID 353429

Reaction equation

HRID 353429 reaction equation
Cl[C:2](=[C:6]([C:9]#[N:10])[C:7]#[N:8])[CH:3]([CH3:5])[CH3:4].Cl.[Cl:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=1[NH:20][NH2:21].C(N(CC)CC)C>C1COCC1>[NH2:8][C:7]1[N:20]([C:14]2[C:13]([Cl:12])=[CH:18][CH:17]=[CH:16][C:15]=2[Cl:19])[N:21]=[C:2]([CH:3]([CH3:5])[CH3:4])[C:6]=1[C:9]#[N:10]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2723909(2,6-Dichlorophenyl)hydrazine monohydrochlorideHCID 23513711(1-Chloro-2-methylpropylidene)propanedinitrile

Product 1

HCID 235137165-Amino-1-(2,6-dichlorophenyl)-3-isopropyl-1H-pyrazole-4-carbonitrileYield 62.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of (1-chloro-2-methylpropylidene)methane-1,1-dicarbonitrile (9.4 g, 61 mmol) in THF (250 mL) was treated with 2,6-dichlorophenylhydrazine hydrochloride (13.0 g, 61 mmol) followed by triethylamine (12.3 g, 122 mmol). The reaction was then heated to reilux for 18 h. The reaction was then cooled to room temp and partitioned between EtOAc (150 mL) and 1N NaOH (100 mL). The aqueous layer was extracted with EtOAc (2×150 mL) and the combined organic layers were washed with 10% aq. citric acid (150 mL), sat. aq. NaHCO3 (150 mL), and brine (150 mL). The organic layer was dried (MgSO4), filtered, and evaporated. The crude product was recrystallized from EtOAc/hexane to yield the desired pyrazole (11.2 g, 62%).

Workup

  1. temperatureThe reaction was then heated
  2. custompartitioned between EtOAc (150 mL) and 1N NaOH (100 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×150 mL)
  4. washthe combined organic layers were washed with 10% aq. citric acid (150 mL), sat. aq. NaHCO3 (150 mL), and brine (150 mL)
  5. dry with materialThe organic layer was dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was recrystallized from EtOAc/hexane

Sources & evidence

ORD record
ord-75ffd4f0abad41cd87f7ac51ad6f9247
Source dataset
uspto-grants-2004_06
Patent number
US06753329B2

Linked notes

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