Triethylamine → 3-methyl-1-(oxan-4-yl)-1H-pyrazol-5-amine

Participants

Reaction Conditions

Reaction Steps

(2Z)-3-Amino-2-butenenitrile (0.538 g, 6.55 mmol), tetrahydro-2H-pyran-4-ylhydrazine (1 g, 6.55 mmol) and triethylamine (0.913 mL, 6.55 mmol) were added to ethanol (300 mL), and the reaction mixture was stirred at 75° C. for 16 hours. The solvent was removed in vacuo, and the crude material suspended in EtOAc. The organic phase was washed with water and then brine. The organic layer was then dried over MgSO4, filtered, and concentrated in vacuo. Half of the crude material was purified by reverse HPLC (mobile phase: 0-30% ACN/H2O, 0.1% TFA) to afford 380 mg of the desired product. The other half of the crude material was purified via silica gel chromatography (eluent: 0% to 100% EtOAc:Hex then 0% to 20% MeOH:DCM). An additional 300 mg of the desired product was obtained (overall yield: 57%). LCMS E-S (M+H)=182.0. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.78 (dd, 2H), 1.94 (qd, J=12.13, 4.55 Hz, 2H), 2.19 (s, 3H), 3.30-3.46 (m, 2H), 3.99 (dd, J=11.49, 4.17 Hz, 2H), 4.49 (m, J=11.65, 11.65, 4.11, 3.92 Hz, 1H), 5.53 (s, 1H).

Provenance & Evidence