2-(Ethoxymethylene)propanedinitrile → 5-amino-1-(3-chloro-2-methylphenyl)-1H-pyrazole-4-carbonitrile

HRID 1098181Notes

Reaction equation

HRID 1098181 reaction equation
Cl.[Cl:2][C:3]1[C:4]([CH3:11])=[C:5]([NH:9][NH2:10])[CH:6]=[CH:7][CH:8]=1.C(O[CH:15]=[C:16]([C:19]#[N:20])[C:17]#[N:18])C>>[NH2:20][C:19]1[N:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([Cl:2])[C:4]=2[CH3:11])[N:10]=[CH:15][C:16]=1[C:17]#[N:18]

Participants

3

Reactant 2

HCID 671522-(Ethoxymethylene)propanedinitrileHCID 12732296(3-Chloro-2-methylphenyl)hydrazine hydrochloride

Product 1

HCID 575046545-amino-1-(3-chloro-2-methylphenyl)-1H-pyrazole-4-carbonitrileYield 58.4%

Conditions

Temperature
0 °C

Procedure

(3-Chloro-2-methylphenyl)hydrazine hydrochloride (CAS no. 65208-12-0) (9 g, 46.61 mmol) was partitioned between EtOAc (100 mL) and NaOH (2M, aq) (60 mL). The organic layer separated and washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated. The resultant oil was suspended in MeOH (100 mL) under nitrogen at −5° C. 2-(Ethoxymethylene)malononitrile (5.69 g, 46.61 mmol) was added portionwise over 5 mins and the mixture stirred at ˜0° C. for 30 mins. The reaction mixture was allowed to warm to room temperature and then heated at reflux under nitrogen for 2 hours. The reaction mixture was allowed to cool and evaporated to dryness. The crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane to afford the product(6.33 g, 58.4%). 1H NMR (400 MHz, DMSO) δ 2.02 (3H, s), 6.57 (2H, s), 7.25-7.32 (1H, m), 7.37 (1H, t), 7.58-7.64 (1H, m), 7.77 (1H); m/z (ES+) (M+H)+=233.28; HPLC tR=1.89 min.

Workup

  1. custom65208-12-0) (9 g, 46.61 mmol) was partitioned between EtOAc (100 mL) and NaOH (2M, aq) (60 mL)
  2. customThe organic layer separated
  3. washwashed with water (50 mL), brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customwas suspended in MeOH (100 mL) under nitrogen at −5° C
  8. temperatureto warm to room temperature
  9. temperatureheated
  10. temperatureat reflux under nitrogen for 2 hours
  11. temperatureto cool
  12. customevaporated to dryness
  13. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 50% EtOAc in isohexane

Sources & evidence

ORD record
ord-7f336540683142958c01003c4689bf8e
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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