Method for preparing 2-[1H-pyrazole-5-radical]-4H-3, 1-benzoxazine-4-ketone compound
A technology of -4H-3 and ketone compounds, applied in the direction of organic chemistry, can solve the problems of dangerous oxidation operation, long steps, large amount of waste water, etc.
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Embodiment 1
[0046] Example 1: Synthesis of 3-chloro-1-(3-chloro-2-pyridyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid
[0047]
[0048] Add 3-chloro-1-(3-chloro-2-pyridyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid ethyl ester (15.90 g, 50.00 mmol ), THF (100 milliliters), water (100 milliliters), sodium hydroxide (3.03 grams, 75.00 millimoles), react at room temperature for 6 hours, remove THF under reduced pressure, add water (50 milliliters) and ethyl acetate (20 milliliters) Extraction, the inorganic phase was acidified to pH = 2 with hydrochloric acid, and then extracted with dichloromethane (75 ml × 3 times), the organic phase was washed with anhydrous MgSO 4 Drying, desolvation under reduced pressure gave 12.68 grams of white crystalline powder, HPLC normalized content was 98% (analysis conditions: chromatographic column is ZORBAX Eclipse XDB-C8 4.6 * 150mm 5 μm, mobile phase is acetonitrile: water=70: 30), m.p. 57-59°C, yield 95%.
[0049] 1 H NMR (300MHz, CDCl 3 ( dd, 1H). ...
Embodiment 2
[0050] Example 2: Synthesis of 3-bromo-1-(3-chloro-2-pyridyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid
[0051]
[0052] Add 3-chloro-1-(3-chloro-2-pyridyl)-4,5-dihydro-1H-pyrazole-5-carboxylic acid ethyl ester (18.50 g, 50.78 mmol ), THF (100 milliliters), water (100 milliliters), sodium hydroxide (3.06 grams, 76.17 millimoles), react at room temperature for 6 hours, remove THF under reduced pressure, add water (50 milliliters) and ethyl acetate (20 milliliters) Extraction, the inorganic phase was acidified to pH = 2 with hydrochloric acid, and then extracted with dichloromethane (75 ml × 3 times), the organic phase was washed with anhydrous MgSO 4 Drying, desolvation under reduced pressure gave 15.25 grams of white crystalline powder, HPLC normalized content was 98% (analysis conditions: chromatographic column is ZORBAX Eclipse XDB-C8 4.6 * 150mm 5 μm, mobile phase is acetonitrile: water=70: 30), m.p.66-68°C, yield 96%.
[0053] 1 H NMR (300MHz, CDCl 3 ( dd, 1H).
...
Embodiment 3
[0055] Example 3: 6-chloro-2-[3-chloro-1-(3-chloro-2-pyridyl)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzene Synthesis of oxazin-4-one
[0056]
[0057] Methanesulfonyl chloride (6.02 g, 52.57 mmol) was added to a 250 ml reaction flask, and 3-chloro-1-(3-chloro-2-pyridyl)-4,5-dihydro-1H-pyrazole was added dropwise -A solution of 5-formic acid (12.68 g, 47.77 mmol), acetonitrile (50 ml) and triethylamine (5.31 g, 52.57 mmol) was reacted at room temperature for 1 hour, and 2-amino-5-chloro-3- Toluic acid (8.87 g, 47.77 mmol), reacted for 30 minutes, added dropwise triethylamine (10.62 g, 105.14 mmol), reacted for 1 hour, added dropwise methanesulfonyl chloride (6.02 g, 52.57 mmol), reacted 6 hours. Stand still, filter, the filter cake is a yellow solid, wash the filter cake with THF (20 ml × 2 times), the filtrate is precipitated under reduced pressure, and column chromatography (ethyl acetate / petroleum ether=1 / 5) gives 7.38 g of a yellow solid , the HPLC normalized content was ...
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