Germicidal composition
A composition and bactericidal technology, which is applied in the field of bactericidal compositions, can solve the problems of low drug susceptibility, effect persistence, etc.
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Embodiment 1
[0449] Example 1: 4-[4-(6,9-difluoro-1,5-dihydro-3H-2,4-benzodioxa -3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)- 1 Preparation of H-pyrazol-1-yl]acetyl]piperidine (compound 1-3)
[0450] 4-(4-formyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1-yl]acetyl]piperidine (210 mg) (compound described in WO2008 / 013622 publication), 3,6-difluoro-1,2-benzenedimethanol (210 mg) and p-toluenesulfon Acid monohydrate (11 mg) was dissolved in toluene (15 mL) and heated to reflux for 1 hour using a Dean-Stark apparatus. After cooling the reaction solution to room temperature, it was diluted with ethyl acetate, and washed with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate, and after the inorganic matter was filtered off, the solvent was distilled off under reduced pressure. The residue was purified using a fast (flash) automatic refining device (Biotage AB / Isolera TM ) silica gel flash chromatography (ethyl acetate-hexane:...
Embodiment 2
[0451] Example 2: 4-[4-(6-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxa -3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)- 1 Preparation of H-pyrazol-1-yl]acetyl]piperidine (compound 1-6)
[0452] 4-(4-formyl-2-thiazolyl)-l-[2-[5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1-yl]acetyl]piperidine (200mg), 3-methylsulfonyloxy-1,2-benzenedimethanol (121mg) and p-toluenesulfonic acid monohydrate (20mg) were dissolved in Toluene (20 mL) was subjected to the same reaction as in the preparation of compound 1-3 and purified to obtain the title compound as a white amorphous solid (298 mg, yield 96%).
Embodiment 3
[0453] Example 3: 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxa -3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)- 1 Preparation of H-pyrazol-1-yl]acetyl]piperidine (compound 1-8)
[0454] 4-(4-formyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)- 1 H-pyrazol-1-yl]acetyl]piperidine (220 mg), 3-fluoro-6-methylsulfonyloxy-1,2-benzenedimethanol (150 mg) and p-toluenesulfonic acid monohydrate ( 20 mg) was dissolved in toluene (15 mL), subjected to the same reaction as in the preparation of compound 1-3, and purified to obtain the title compound as a white amorphous solid (297 mg, yield 84%). Methanol was added to the obtained resin, dissolved under reflux under heating, and then left to stand at room temperature to obtain a white solid (melting point: 151° C.).
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