Lomerizine Hydrochloride isomeride and preparation method therefor

A technology of lomerizine hydrochloride isomers and isomers, which is applied in the field of lomerizine hydrochloride isomers and its preparation, can solve the problem of obtaining lomerizine hydrochloride isomers and hydrochloric acid which have not yet been found. Difficult separation of isomers of lomerizine and other problems

Inactive Publication Date: 2015-12-23
四川省百草生物药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] In the synthesis technique of lomerizine hydrochloride, the isomers of lomerizine hydrochloride may be produced, but due to the limitation of the reaction itself, the isomers of lomerizine hydrochloride are difficult to separate; Lizine isomers need to be obtained through special reactions, but no method has been found to obtain lomerizine hydrochloride isomers

Method used

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  • Lomerizine Hydrochloride isomeride and preparation method therefor
  • Lomerizine Hydrochloride isomeride and preparation method therefor
  • Lomerizine Hydrochloride isomeride and preparation method therefor

Examples

Experimental program
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Embodiment 1

[0037] Add 21.8g of compound II 2,4'-difluorobenzophenone into the flask, then add 50ml of anhydrous methanol and 3.8g of sodium borohydride, and react at -10~-5°C for 5 hours. After the reaction is completed, Add 20ml of dichloromethane to the reaction solution to extract twice, collect the extract, add anhydrous sodium sulfate to the extract and dry for 6 hours, then concentrate under reduced pressure at 40°C to remove the organic solvent, dichloromethane, to obtain 22g of compound III 2,4 '-difluorobenzhydryl alcohol;

[0038] Add 22g of compound III and 8ml of thionyl chloride into the flask, add 1 drop of N,N-dimethylformamide dropwise, and react at 80°C for 6 hours. After the reaction is completed, concentrate under reduced pressure at this temperature to remove Thionyl chloride was obtained to obtain compound IV 2,4'-difluorodiphenylchloromethane; then the obtained compound IV 2,4'-difluorodiphenylchloromethane, 10g benzyltriethylammonium chloride, 7.5g piperazine , 10...

Embodiment 2

[0058] Add 21.8g of compound II 2,4'-difluorobenzophenone into the flask, then add 50ml of absolute ethanol and 5.7g of sodium borohydride, and react at -8~-3°C for 4 hours. After the reaction is completed, Add 20ml of dichloromethane to the reaction solution to extract 3 times, collect the organic phase, add anhydrous sodium sulfate to the organic phase and dry for 8 hours, then concentrate under reduced pressure at 40°C to remove the organic solvent, dichloromethane, to obtain 22.5g of compound III 2 ,4'-difluorobenzhydryl alcohol;

[0059] Add 22.5g of compound III and 8.2ml of thionyl chloride into the flask, drop 1 drop of N,N-dimethylformamide, and react at 80°C for 4 hours. After the reaction is completed, depressurize at this temperature Concentrate to remove thionyl chloride to obtain compound IV 2,4'-difluorodiphenylchloromethane; then the obtained compound IV 2,4'-difluorodiphenylchloromethane, 10g benzyltriethylammonium chloride, 8.2g Add piperazine, 103ml of tolu...

Embodiment 3

[0064] Add 21.8g of compound II 2,4'-difluorobenzophenone to the flask, then add 50ml of absolute ethanol and 4.75g of sodium borohydride, and react at -5 to 0°C for 4 hours. After the reaction is completed, the reaction Add 20ml of dichloromethane to the liquid and extract 3 times, collect the extract, add anhydrous sodium sulfate to the extract and dry for 7 hours, then concentrate under reduced pressure at 50°C to remove the organic solvent dichloromethane to obtain 22.8g of compound III 2,4 '-difluorobenzhydryl alcohol;

[0065] Add 22.8g of compound III and 8.2ml of thionyl chloride into the flask, drop 1 drop of N,N-dimethylformamide, and react at 70°C for 6 hours. After the reaction is completed, decompress at this temperature Concentrate to remove thionyl chloride to obtain compound IV 2,4'-difluorodiphenylchloromethane; then the obtained compound IV 2,4'-difluorodiphenylchloromethane, 10g benzyltriethylammonium chloride, 8.3g Add piperazine, 110ml of toluene and 100m...

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Abstract

The invention relates to a lomerizine Hydrochloride isomeride and a preparation method therefor. The structural formula of the lomerizine Hydrochloride isomeride is shown in the specification. The chemical name is 1-(2,4'-difluoro benzhydryl)-4-[(2,3,4- trimethoxyphenyl)methyl]piperazine hydrochloride. 2,4'-difluoro benzhydryl ketone is subjected to reduction and halogenation, halogen substitution is carried out by utilization of piperazine, the obtained compound and 2,3,4- trimethoxy benzaldehyde are subjected to a condensation reaction, finally a salt forming reaction with concentrated hydrochloric acid is carried out, and the lomerizine Hydrochloride isomeride is prepared.

Description

technical field [0001] The invention relates to a lomerizine hydrochloride isomer and a preparation method thereof. Background technique [0002] Lomerizine hydrochloride is a new type of calcium channel blocker, which is mainly used for the treatment of migraine. Compared with flunarizine hydrochloride, it has better therapeutic effect and fewer side effects in the short term, and it has a better effect on cerebrovascular The selectivity is better, the effect on increasing cerebral blood flow and protecting brain tissue is stronger, and the impact on the heart is relatively small, and it has its unique advantages in the treatment and prevention of migraine. [0003] In the synthesis technique of lomerizine hydrochloride, the isomers of lomerizine hydrochloride may be produced, but due to the limitation of the reaction itself, the isomers of lomerizine hydrochloride are difficult to separate; Lizine isomers need to be obtained through special reactions, but no method for ob...

Claims

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Application Information

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IPC IPC(8): C07D295/096
CPCC07D295/096
Inventor 罗益民杨文
Owner 四川省百草生物药业有限公司
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