(2Z)-3-Amino-2-butenenitrile → 1-Cyclobutyl-3-methyl-1H-pyrazol-5-amine
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]1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
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, 2H) 2.21 (s, 3H) 2.32-2.43 (m, 2H) 2.69 (ddd, J=10.55, 9.41, 2.53 Hz, 2H) 3.26-3.55 (br s, 2H) 4.48-4.59 (m, 1H) 5.36 (s, 1H)