(2Z)-3-Amino-2-butenenitrile → 1-Cyclobutyl-3-methyl-1H-pyrazol-5-amine

HRID 1522420Notes

Reaction equation

HRID 1522420 reaction equation
N/[C:2](/[CH3:6])=[CH:3]\[C:4]#[N:5].Cl.[CH:8]1([NH:12][NH2:13])[CH2:11][CH2:10][CH2:9]1>C(O)C>[CH:8]1([N:12]2[C:4]([NH2:5])=[CH:3][C:2]([CH3:6])=[N:13]2)[CH2:11][CH2:10][CH2:9]1

Participants

4

Reactant 2

HCID 5325263(2Z)-3-Amino-2-butenenitrileHCID 19432792Cyclobutylhydrazine--hydrogen chloride (1/1)

Product 1

HCID 566043711-Cyclobutyl-3-methyl-1H-pyrazol-5-amine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

(2Z)-3-Amino-2-butenenitrile (1.339 g, 16.31 mmol) and cyclobutylhydrazine HCl (2 g, 16.31 mmol) were added to ethanol (20 mL) and heated at 75° C. for 16 h. After cooling to room temperature, the solvent was removed under reduced pressure. The crude residue was suspended in saturated NaHCO3 (30 mL) and EtOAc (50 mL), and stirred for 10 min. The phases were separated and the aq. phase extracted with EtOAc (3×50 mL). The combined EtOAc extracts were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was purified via silica gel chromatography (eluent: 0 to 5% EtOAc:DCM, then gradient to 100% EtOAc). The final product was collected as 0.4 g (16%). LCMS E-S (M+H)=:152.0. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.67-2.00 (m, 2 H) 2.21 (s, 3 H) 2.32-2.43 (m, 2 H) 2.69 (ddd, J=10.55, 9.41, 2.53 Hz, 2 H) 3.26-3.55 (br s, 2 H) 4.48-4.59 (m, 1 H) 5.36 (s, 1 H)

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe solvent was removed under reduced pressure
  3. customThe phases were separated
  4. extractionthe aq. phase extracted with EtOAc (3×50 mL)
  5. washThe combined EtOAc extracts were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude residue was purified via silica gel chromatography (eluent
  10. customThe final product was collected as 0.4 g (16%)

Sources & evidence

ORD record
ord-82c7bd9617164d64a4375ec7f60a6204
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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