A kind of moxifloxacin hydrochloride structural analogue and preparation method thereof
A technology similar to moxifloxacin hydrochloride and its structure, which is applied in the field of new moxifloxacin hydrochloride structural analogs and its preparation, can solve the problems of the impact on the safety and effectiveness of the final drug delivery and the increase of impurity content, so as to ensure safety and reliability, The effect of simple operation and mild reaction conditions
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Embodiment 1
[0035] Embodiment 1: the preparation of compound II
[0036] Add 57.0g of 2-cyclopentenone, 165.0g of N-methoxymethyl-N-trimethylsilylmethyl-benzylamine, and 750ml of DCM into a 1L three-necked flask, stir and cool. Slowly add 180ml of TFA dropwise, and control the internal temperature at -5~0°C. After the dropwise addition is completed, the temperature is raised, and the reaction is monitored by TLC until the end point. Pour the reaction solution into a pre-prepared 2M sodium hydroxide (3750ml) solution, add DCM (300ml*2) for extraction, combine the organic layers, dry over anhydrous magnesium sulfate, filter with suction, and concentrate under reduced pressure to obtain a brown oil (II) .
Embodiment 2
[0037] Embodiment 2: the preparation of compound III
[0038] Add 149.61g 2-benzylhexahydrocyclopenta[C]pyrrol-4-(1H)-one (II), 72.47g hydroxylamine hydrochloride, 144.07g potassium carbonate, 1500ml methanol and 52.5ml water in a 3L three-necked flask, Raise the temperature to reflux, stir, and monitor the reaction to the end point by TLC. After cooling to room temperature, it was filtered with suction, and the filtrate was concentrated under reduced pressure until no liquid dripped out. Add 800ml of water to the concentrated oil, extract with DCM (800ml*2), combine the organic phases, and dry over anhydrous magnesium sulfate. Suction filtration and concentration under reduced pressure gave 153.0 g of a brown oil, which was decolorized to give a white solid, namely compound III.
Embodiment 3
[0039] Embodiment 3: the preparation of compound IV
[0040] Add 17.42g of 2-benzylhexahydrocyclopenta[C]pyrrole-4-(1H)-ketoxime (Ⅲ), 8.71g of sodium hydroxide, 430ml of acetone and 160ml of water into a 1L three-necked flask, and divide Add 20.20 g of p-toluenesulfonyl chloride in batches, after the addition is complete, stir the reaction, and monitor the reaction to the end point by TLC. The reaction solution was extracted with DCM (250ml*2), the organic layers were combined, dried over anhydrous magnesium sulfate, filtered with suction, and concentrated under reduced pressure until there was no liquid drop, and 59.81g of a brown oil was obtained.
[0041] Add 42ml of glacial acetic acid and 42ml of acetic anhydride to the oil obtained above, stir, and monitor the reaction to the end point by TLC. Add 210ml of water, wash with ethyl acetate (50ml*2), adjust the pH of the water phase to 12-14 with 15% sodium hydroxide solution, wash with petroleum ether (50ml*3), and wash th...
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