A method for reclaiming piperazine after the piperazine reduction reaction in the preparation of quinolone medicines

A quinolone and post-reaction technology, applied in the field of chemical pharmaceuticals, can solve problems such as unsuitable for industrial production and use, achieve great application value, reduce waste gas, and improve the effect of operating environment

Active Publication Date: 2015-07-29
ZHEJIANG JINGXIN PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Therefore, said method is not suitable for suitability for suitability for suitability for industrialized production use

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  • A method for reclaiming piperazine after the piperazine reduction reaction in the preparation of quinolone medicines

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Experimental program
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Effect test

Embodiment 1

[0020] Take 30 grams (0.11 moles) of cyclopropanecarboxylic acid (i.e. 1-cyclopropyl-6-fluoro-7-chloro-4-oxo-1,4-dihydro-3-quinoline carboxylic acid), according to the literature Method (Tetra. Lett. 1996, 37, 6785, etc.) and 60 grams of anhydrous piperazine (0.70 moles) were reacted with piperazine. During the reaction, 32 grams of purified water and 3 grams of aluminum acetate were added, and reflux at 110 ° C for 8 hours to prepare Obtained piperazine reaction solution, after the reaction, add 35 grams of 30% sodium hydroxide aqueous solution, stir and react for 0.5 hour, then reduce the pressure to -0.01Mpa, heat up to 115-120°C to recover piperazine, and after recovery for 2 hours, basically No material was evaporated, and the vacuum was increased to -0.09MPa, and recovered for 15 minutes. The recovered material system became powdery, and 115.4 grams of recovered material were obtained, which contained 48.69 grams (0.57 moles) of piperazine, and the recovery rate was 96.6%...

Embodiment 2

[0024] Take 30 grams (0.11 moles) of cyclopropanecarboxylic acid (i.e. 1-cyclopropyl-6-fluoro-7-chloro-4-oxo-1,4-dihydro-3-quinoline carboxylic acid), according to the literature Methods (Tetra.Lett.1996, 37, 6785, etc.) react with anhydrous piperazine 60 grams (0.70 moles) to prepare the piperidine reaction solution, add 30% potassium hydroxide aqueous solution 32 grams, stir for 0.5 hours, and then Reduce the pressure to -0.02Mpa, raise the temperature to recover piperazine, after recovering for 1.5 hours, basically no material is evaporated, increase the vacuum to -0.09MPa, recover for 30 minutes, the system becomes powdery, and obtain 112.7 grams of recovered product, which contains 45.71 g of piperazine g (0.55 mol), the recovery rate was 90.1%.

[0025] MS(ESI):m / z=87[M+H + ] confirmed that the recovery was piperazine;

[0026] The recovered materials were salted and refined according to the literature method to obtain 31.04 g of ciprofloxacin hydrochloride finished pr...

Embodiment 3

[0028] Take 30 grams (0.11 moles) of cyclopropanecarboxylic acid (i.e. 1-cyclopropyl-6-fluoro-7-chloro-4-oxo-1,4-dihydro-3-quinoline carboxylic acid), according to the literature Method (Tetra.Lett.1996, 37, 6785, etc.) reacted with anhydrous piperazine 60 grams (0.70 moles) to prepare the piperidine reaction solution, added 48 grams of 50% sodium carbonate aqueous solution, stirred for 0.5 hours, and then reduced Press down to -0.03Mpa, raise the temperature to recover piperazine, after recovering for 1.5 hours, basically no material is evaporated, increase the vacuum to -0.09MPa, recover for 15 minutes, the system becomes powdery, and obtain 117.2 grams of recovered product, which contains 47.62 grams of piperazine (0.55 mol), the recovery rate was 93%.

[0029] MS(ESI):m / z=87[M+H + ] confirmed that the recovery was piperazine;

[0030] The recovered materials were salted and refined according to the literature method to obtain 31.04 g of ciprofloxacin hydrochloride finish...

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Abstract

The invention relates to the chemical pharmaceutical technology, and provides a method for recovering piperazine after a piperazine condensation reaction in the quinolone medicine preparation. The method comprises a step of adding an inorganic base after the piperazine condensation reaction is finished, and a step of carrying out reduced pressure recovery of piperazine. Compared with the prior art, the method provided by the invention has the following advantages: 1, the piperazine recovery rate is high and can reach above 90%, the introduction of other organic solvents is effectively reduced, the unit consumption of high boiling point solvents and the relevant cost are also effectively reduced, and the discharge of exhaust gas and wastewater is substantially reduced; and 2, the conversion of free quinolone into its alkali metal salt weakens interaction forces comprising a hydrogen bond, an ionic bond and the like between a quinolone compound and piperazine, so piperazine can be steamed out from a system, the unit consumption of piperazine decreases by 15-20%, and the recovery time decreases by 25%, thereby the energy consumption is correspondingly reduced. The method is simple, is suitable for the industrial production and has large application values.

Description

technical field [0001] The invention relates to the field of chemical pharmacy, in particular to a method for recovering and applying bipiperazine in the preparation of quinolones. Background technique [0002] Quinolones such as Norfloxacin (Norfloxacin), Ciprofloxacin (Ciprofloxacin), Sarafloxacin (Sarafloxacin) (hereinafter referred to as "floxacin") or their hydrates or their acid salts; quinolones are The synthetic antibacterial drug containing 4-quinolone core has selective inhibitory effect on bacterial DNA helicase (DNA-gyrase), thereby inhibiting bacterial DNA synthesis, leading to DNA degradation and death. This type of drug has been widely used clinically because of its broad antibacterial spectrum, strong antibacterial activity, and few adverse reactions (according to the latest reports, some varieties have broken through the concept of antibacterial, and have made new progress in antiviral and antitumor aspects). And it has become a hot drug that many pharmaceu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D295/023C07D295/027C07D215/56
Inventor 孙海林金志平罗少华吴源
Owner ZHEJIANG JINGXIN PHARMA
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