Example 375-Methyl-2H-pyridazin-3-one 5-Hydroxy-4-methyl-5H-furan-2-one (10.0 g, 87.6 mmol) and hydrazine hydrate (4.38 g, 87.6 mmol) were stirred vigorously at room temperature for 1.5 hours in tetrahydrofuran. A solid began to precipitate and the reaction was heated at 60° C. overnight. The crude reaction mixture was concentrated onto silica gel and purified by column chromatography (0 to 10percent methanol in 1:1 EtOAc/dichloromethane) to give 7.7 g (80percent) of the title compound.1H NMR (300 MHz, CDCl3): δ (ppm) 11.38 (broad s, 1H), 7.66 (s, 1H), 6.74 (s, 1H), 2.25 (s, 3H).
80%
With hydrazine In tetrahydrofuran at 20 - 60℃;
5-Methyl-2H-pyridazin-3-one γγ°5-Hydroxy-4-methyl-5H-furan-2-one (10.0 g, 87.6 mmol) and hydrazine hydrate (4.38 g, 87.6 mmol) were stirred vigorously at r.t. for 1.5 hours in tetrahydrofuran. A solid began to precipitate and the reaction was heated at 60 °C overnight. The crude reaction mixture was concentrated onto silica gel and purified by column chromatography (0 to 10 percent methanol in 1 :1 EtOAc / dichloromethane) to give 7.7 g (80 percent) of the title compound. 1H NMR (300 MHz, CDCl3) δ 11.38 (br, IH), 7.66 (s, IH), 6.74 (s, IH), 2.25 (s, 3H).
80%
With hydrazine In tetrahydrofuran at 20 - 60℃;
5-Methyl-2H-pyridazin-3-one γγ°5-Hydroxy-4-methyl-5H-furan-2-one (10.0 g, 87.6 mmol) and hydrazine hydrate (4.38 g, 87.6 mmol) were stirred vigorously at r.t. for 1.5 hours in tetrahydrofuran. A solid began to precipitate and the reaction was heated at 60 °C overnight. The crude reaction mixture was concentrated onto silica gel and purified by column chromatography (0 to 10 percent methanol in 1 :1 EtOAc / dichloromethane) to give 7.7 g (80 percent) of the title compound. 1H NMR (300 MHz, CDCl3) δ 11.38 (br, IH), 7.66 (s, IH), 6.74 (s, IH), 2.25 (s, 3H).
Reference：
[1] Patent: US2007/259860, 2007, A1, . Location in patent: Page/Page column 31
[2] Patent: WO2008/41075, 2008, A1, . Location in patent: Page/Page column 54
[3] Patent: WO2008/41075, 2008, A1, . Location in patent: Page/Page column 54
[4] Journal of Organic Chemistry, 1981, vol. 46, # 24, p. 4889 - 4894
[5] Journal of Organic Chemistry, 1981, vol. 46, # 24, p. 4889 - 4894
2
[ 616-02-4 ]
[ 931-23-7 ]
[ 40834-42-2 ]
Yield
Reaction Conditions
Operation in experiment
60%
With lithium tri-t-butoxyaluminum hydride In tetrahydrofuran at -30 - -15℃; for 3 h; Inert atmosphere
A solution of 5.34 g LiAlH(t-BuO)3 (21.00 mmol) in 40 cm3 anhydrous THF was added dropwise over a 30-min period to a solution of 1.68 g citraconic anhydride (6, 15.00 mmol) in 50 cm3 anhydrous THF under a nitrogen atmosphere at - 30 C. The temperature was maintained at - 15 C for 3 h and then the reaction mixture was warmed to ambient temperature. The reaction was quenched with 50 cm3 1 M HCl, the solution was saturated with NaCl, the crude product was extracted with EtOAc (3 9 50 cm3), and the combined organic fraction was dried over MgSO4. The solvent was removed in vacuo. Purification by column chromatography (SiO2, 20percent AcOEt in petroleum ether) afforded 7a (1.023 g,60percent) and 7b (116 mg, 7percent) as yellow oils. TLC: Rf = 0.16 (for 7a), 0.15 (for 7b) (20percent AcOEt in petroleum ether). 7a: 1H NMR (400 MHz, acetone-d6): d = 6.67 (bs, 1H),6.02 (bs, 1H), 5.87 (p, J = 1.5 Hz, 1H), 2.08 (d,J = 1.5 Hz, 3H) ppm; 13C NMR (100 MHz, acetone-d6):d = 171.30 ([C\), 166.65 ([C\), 118.68 (CH), 100.25(CH), 13.15 (CH3) ppm; MS (EI): m/z (percent) = 114.0 ([M?],2), 113.0 (7), 86.0 (61), 85.0 (13), 69.0 (100), 68.0 (82),41.1 (50), 40.1 (65), 39.1 (93).
Example 375-Methyl-2H-pyridazin-3-one 5-Hydroxy-4-methyl-5H-furan-2-one (10.0 g, 87.6 mmol) and hydrazine hydrate (4.38 g, 87.6 mmol) were stirred vigorously at room temperature for 1.5 hours in tetrahydrofuran. A solid began to precipitate and the reaction was heated at 60 C. overnight. The crude reaction mixture was concentrated onto silica gel and purified by column chromatography (0 to 10% methanol in 1:1 EtOAc/dichloromethane) to give 7.7 g (80%) of the title compound.1H NMR (300 MHz, CDCl3): delta (ppm) 11.38 (broad s, 1H), 7.66 (s, 1H), 6.74 (s, 1H), 2.25 (s, 3H).
80%
With hydrazine; In tetrahydrofuran; at 20 - 60℃;
5-Methyl-2H-pyridazin-3-one gammagamma5-Hydroxy-4-methyl-5H-furan-2-one (10.0 g, 87.6 mmol) and hydrazine hydrate (4.38 g, 87.6 mmol) were stirred vigorously at r.t. for 1.5 hours in tetrahydrofuran. A solid began to precipitate and the reaction was heated at 60 C overnight. The crude reaction mixture was concentrated onto silica gel and purified by column chromatography (0 to 10 % methanol in 1 :1 EtOAc / dichloromethane) to give 7.7 g (80 %) of the title compound. 1H NMR (300 MHz, CDCl3) delta 11.38 (br, IH), 7.66 (s, IH), 6.74 (s, IH), 2.25 (s, 3H).
5-ethylcarbonyloxy-4-methyl-1-(5-chloro-4-trifluoromethylpyridin-2-yl)-1,5-dihydro-2H-pyrrol-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
No. I.5-451: 5-Ethylcarbonyloxy-4-methyl-1-(5-chloro-4-trifluoromethylpyridin-2-yl)-1,5-dihydro-2H-pyrrol-2-one 5-Hydroxy-4-methyl-2,5-dihydrofuran-2-one (300 mg, 2.63 mmol, 1.0 equiv) and <strong>[1095823-39-4]2-amino-5-chloro-4-trifluoromethylpyridine</strong> (568 mg, 2.89 mmol, 1.1 equiv) were dissolved in abs. toluene (12 ml) and stirred under reflux conditions for 16 h. After cooling to room temperature, the reaction mixture was filtered off with suction and, after thorough drying, 5-(5-chloro-4-trifluoromethylpyridin-2-yl)amino-4-methyl-2,5-dihydrofuran-2-one was isolated without any further purification in the form of a colorless solid (530 mg, 68% of theory).). 1H-NMR (400 MHz, d6-DMSO delta, ppm) 8.43 (s, 1H), 8.36 (d, 1H), 7.06 (s, 1H), 6.78 (d, 1H), 6.15 (m, 1H), 2.07 (s, 3H). 5-(5-Chloro-4-trifluoromethylpyridin-2-yl)amino-4-methyl-2,5-dihydrofuran-2-one (250 mg, 0.85 mmol, 1.0 equiv) was dissolved in propionic anhydride (2.22 g, 20 equiv) and stirred at a temperature of 155 C. for 4 h. After cooling to room temperature, the reaction mixture was filtered off with suction, and final purification by column chromatography of the resulting crude product (gradient ethyl acetate/heptane) gave 5-ethylcarbonyloxy-4-methyl-1-(5-chloro-4-trifluoromethylpyridin-2-yl)-1,5-dihydro-2H-pyrrol-2-one in the form of a colorless solid (35 mg, 12% of theory). 1H-NMR (400 MHz, CDCl3 delta, ppm) 8.67 (s, 1H), 8.39 (s, 1H), 7.42 (s, 1H), 6.02 (m, 1H), 2.39-2.32 (m, 2H), 2.08 (s, 3H), 1.17 (t, 3H).
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