3-methyl-1-(pyridin-4-yl)-4,5-dihydro-1H-pyrazol-5-one synthesis

Yield:111988-01-3 130 mg

Reaction Conditions:

in ethanol at 0 - 60;Inert atmosphere;

Steps:

Intermediate 22

To a solution of ethyl acetoacetate (0.45 mL, 3.5 mmol) in anhydrous ethanol (5.0 mL) was added dropwise a solution of 4-pyridylhydrazine (0.35 mL, 3.5 mmol) at 0 °C. The reaction was allowed to be warmed up to room temperature and stirred for 3-5 hrs. The mixture was further heated at 60^oC overnight. The suspension was concentrated to dryness and the resulting crude product was purified by Teledyne-Isco flash system by using CH₂Cl₂/MeOH, 0 to 5% of methanol in dichloromethane to provide intermediate 22 as a light yellow solid (130 mg).¹H NMR (400 MHz, DMSO-d₆) δ (ppm): 8.78 (d, J = 6.8 Hz, 2H), 6.90 (d, J = 6.4 Hz, 2H), 5.52 (s, 1H), 2.19 (s, 3H). MS (ESI): Calcd. for C9H9N3O: 175, found 176 (M+H)⁺.

References:

WO2016/205460,2016,A1 Location in patent:Paragraph 0176-0177