A kind of medicine for treating pneumonia and preparation method thereof
A technology of pneumonia and drugs, applied in the field of medicine, to achieve excellent results, strong antibacterial activity, and short routes
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preparation example 1
[0037] Preparation 1: 7-(4-fluorobenzyloxy)-4,5-dihydrotetrazole[1,5-a]quinoline (Compound 1)
[0038]
[0039] Step 1: Add 3,4-dihydroquinolin-2(1H)-one (5.0mmol) and triphenylphosphine (20.0mmol), diethyl azodicarboxylate (20.0mmol) to THF (30mL) 1-butyl-3-methyl-imidazolium hexafluorophosphoric acid (2 mL) was added, and then diphenylphosphoryl azide (20.0 mmol) was added, and the mixture was stirred at 40° C. for 15 hours, and the progress of the reaction was monitored by TLC. After the reaction was complete, the reaction solution was cooled to room temperature and diluted with water (50mL), then extracted with ethyl acetate (80mL×3) and the combined extracts were washed with saturated aqueous sodium bicarbonate solution, and the organic layer was washed with anhydrous sulfuric acid Sodium dried and concentrated. The residue was purified by flash chromatography on a silica gel column, using petroleum ether:dichloromethane (v:v=10:1) as the eluting solvent to obtain 4,5...
preparation example 2
[0047] Preparation 2: 7-(4-Chlorobenzyloxy)-4,5-dihydrotetrazole[1,5-a]quinoline (Compound 2)
[0048]
[0049] Step 1 and Step 2 are the same as Preparation Example 1.
[0050] Step 3: Mix 7-bromo-4,5-dihydrotetrazolo[1,5-a]quinoline (2.0mmol), (4-chloro-phenyl)-methanol (2.2mmol), palladium acetate (0.2 mmol), cesium carbonate (4.0 mmol) and 2-dicyclohexylphosphine-2,4,6-triisopropylbiphenyl (0.4 mmol) were added to toluene (30 mL), and stirred for 5 minutes under nitrogen protection. Then it was heated to 85° C. under sealed condition and reacted for 5 hours. After filtration and concentration under reduced pressure, the residue was purified by flash chromatography on a silica gel column, using cyclohexane:ethyl acetate (v:v=7:1) as the eluting solvent, and the main fractions were collected and evaporated to dryness under reduced pressure, and then weighed with ethanol Crystallization gave 0.52 g of the target product.
[0051] Melting point: 188-190°C;
[0052] MS m...
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