Pyridezinone-group-containing butenolide compounds and use thereof
A technology of pyridazinone butenyl lactone and compound, applied in the field of chemistry
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Embodiment 1
[0180] Example 1: Preparation of intermediate 3-(1-hydroxyethyl)-4-phenyl-1-oxaspiro[4.5]dec-3-en-2-one
[0181] The intermediate 3-acetyl-4-phenyl-1-oxaspiro[4.5]dec-3-en-2-one (2.70 g, 0.01 mol) was dissolved in 30 mL of ethanol, and NaBH was added thereto 4 (0.57g, 0.015mol), stirred at room temperature for 1h, after the reaction was monitored by TLC, the solvent was evaporated under reduced pressure, then extracted with ethyl acetate and water, the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and reduced Press precipitation to obtain 2.50 g of a white solid with a melting point of 114-115°C and a yield of 92%. 1 H NMR (600MHz, CDCl 3 )δ:0.95-1.95+1.64-1.79(m,10H,cyclohexyl-10H),1.40(d,J=6.6Hz,3H,CH 3 ), 3.07(d, J=9.6Hz, 1H, OH), 4.37(q, 1H, CH), 7.13-7.15(m, 2H, Ph-3, 5-2H), 7.44-7.45(m, 3H, Ph-2,4,6-3H); 13 C NMR (CDCl 3 ,150MHz)δ:21.91,23.12,24.23,33.21(J=68.7Hz),63.14,88.53,127.35,128.70,129.09,129.90,131.28,166.0...
Embodiment 2
[0182] Example 2: Preparation of intermediate 3-(1-chloroethyl)-4-phenyl-1-oxaspiro[4.5]dec-3-en-2-one
[0183] The intermediate 3-(1-hydroxyethyl)-4-phenyl-1-oxaspiro[4.5]dec-3-en-2-one (2.72 g, 0.01 mol) was dissolved in 20 mL of dichloromethane, Thionyl chloride (1 mL) was added dropwise under ice bath, then stirred at room temperature for 2 h, after the reaction was monitored by TLC, the solvent and excess thionyl chloride were evaporated under reduced pressure, water and ethyl acetate were added thereto for extraction, and the organic phase was Wash with saturated brine, dry over anhydrous magnesium sulfate, filter, and precipitate under reduced pressure to obtain 2.61 g, a white solid, melting point 126-127°C, yield 90% 250 . 1 HNMR (600MHz, CDCl 3 )δ: 1.05-1.11+1.55-1.82(m, 10H, cyclohexyl-10H), 1.71(d, J=7.2Hz, 3H, CH 3 ), 4.63(q,H,CH),7.19-7.21(m,2H,Ph-3,5-2H),7.47-7.48(m,3H,Ph-2,4,6-3H); 13 CNMR (CDCl 3 ,150MHz)δ:21.77,22.42,24.23,33.12(J=21.6Hz),48.42,87.48,127...
Embodiment 3
[0184] Example 3: Compound 2-tert-butyl-4-chloro-5-(1-(2-oxo-4-phenyl-1-oxaspiro[4.5]dec-3-en-3-yl)ethane Preparation of oxy)pyridazin-3(2H)-one (compound 8-9)
[0185] 3-(1-hydroxyethyl)-4-phenyl-1-oxaspiro[4.5]dec-3-en-2-one (2.72g, 0.01mol), potassium carbonate (1.66g, 0.01 2mol) , 2-tert-butyl-4,5-dichloropyridazin-3(2H)-one (commercially available, 2.42g, 0.011mol), dissolved in 20mLN,N-dimethylformamide, the reaction mixture was heated at 80 After reaction at ℃ for 1 h, TLC monitored the completion of the reaction, added ethyl acetate and water for extraction, washed the organic phase with saturated brine, dried over anhydrous magnesium sulfate, filtered, and precipitated under reduced pressure, and the residue was column chromatographed (eluent was ethyl acetate Ester and petroleum ether (boiling range 60-90°C, volume ratio 1:4) to obtain compound 8-9, 2.87g, colorless oil, yield 63% 254 . 1 H NMR (300MHz, CDCl 3 )δ:0.80-1.90(m,10H,cyclohexyl-10H),1.58(d,J=6.6Hz,3H,...
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