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Duloxetine derivative and preparation thereof

A technique for duloxetine and its derivatives, which is applied in the field of duloxetine derivatives and its preparation, can solve the problems of long drug lag period, poor tolerance and safety, poor curative effect, etc., and achieves simple and fast preparation process easy-to-use effects

Inactive Publication Date: 2009-04-22
HEBEI UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This new product has several actions that work together like it's making an anti-depression drug with fewer side effectings than existing products or without them altogether. It makes this way easier to use because there aren’t any extra steps needed beforehand.

Problems solved by technology

This patents discusses various methods for developing effective treatments against anxiety related diseases like major depressed patients who suffer from severe stressors due to lacking quicker acting medications without causing delays during treatment periods. Current therapies often cause unwanted side effects including sedatives and other negative aspects associated therewith. There exists a challenge towards discovering small but safe yet fast-acting agents able to provide faster and longer lastings than current ones while also reducing dosage issues over time.

Method used

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  • Duloxetine derivative and preparation thereof
  • Duloxetine derivative and preparation thereof
  • Duloxetine derivative and preparation thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Example 1: 4-methylbenzoacryloyl chloride

[0022] Add p-methylcinnamic acid (9.732g, 0.06mol) and 2 drops of N,N-dimethylformamide (DMF) into the three-necked flask, add 100ml of toluene as a solvent, slowly drop (14.2752g, 0.12mol) chlorinated For sulfoxide, the temperature was slowly raised to 100°C and refluxed for 3 hours, vacuum rotary evaporation (vacuum degree 10mmHg, the same as the following examples) to remove toluene and excess thionyl chloride, oil pump vacuum distillation to collect 135-136°C / 5mmHg components 10.306 g of white solid was obtained with a yield of 95.0%. mp: 60-62°C.

[0023] IR(KBr)v(cm -1 ): 3085, 2923, 1741, 1601, 1510, 806, 771.

Embodiment 2

[0024] Example 2: 4-methoxyphenylacryloyl chloride

[0025] Add p-methoxycinnamic acid (21.381g, 0.12mol) to the three-necked flask, catalytic amount of N,N-dimethylformamide (DMF), solvent toluene 160ml, slowly dropwise add thionyl chloride (28.554g, 0.24 mol), the temperature was slowly raised to 100°C and refluxed for 3 hours, toluene and excess thionyl chloride were removed by vacuum rotary evaporation, and the 144-145°C / 2mmHg fraction was collected by oil pump vacuum distillation to obtain 22.286 g of bright yellow solid, with a yield of 93.942 %. mp: 40-44°C.

[0026] IR(KBr)v(cm -1 ): 3052, 2844, 1688, 1600, 1514, 862, 775.

Embodiment 3

[0027] Example 3: 4-chlorophenylacryloyl chloride

[0028] Add p-chlorocinnamic acid (18.204g, 0.10mol) in the three-necked flask, catalytic amount of N,N-dimethylformamide (DMF), solvent toluene 100ml, slowly add thionyl chloride (23.793g, 0.2mol) dropwise , the temperature was slowly raised to 100°C and refluxed for 3 hours, the toluene and excess thionyl chloride were removed by vacuum rotary evaporation, and the 118-120°C / 3mmHg fraction was collected by oil pump vacuum distillation to obtain 19.301g of white solid with a yield of 96.55%. mp: 61-63°C. IR(KBr)v(cm -1 ): 3034, 2970, 1699, 1592, 1490, 846, 736.

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PUM

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Abstract

The invention relates to a duloxetine derivative and a method for preparing the same, which belongs to the chemistry field of medicine with antidepressant activity. The structural formula is as shown in the right formula, wherein R is aryl radical or tertiary butyl. The method for preparing the duloxetine derivative comprises the following steps: step one, dissolving duloxetine in dichloromethane in a reactor, adding an acid-binding agent into the mixture, stirring the mixture at room temperature for 20 minutes, and then dripping chloroacetic chloride into the mixture to react at a temperature of between 0 and 30 DEG C for 1 to 5 hours to generate an amide compound 1; and step two, dissolving the amide compound 1 generated in the step one in acetonitrile in the reactor, adding sodium iodide and triethylamine into the mixture of which the mol ratio of the amide compound 1 to the odium iodide to the triethylamine is 1 to 0.003 to (1.5 to 3), and then adding a piperazine compound into the mixture of which the mol ratio of the amide compound 1 to the piperazine compound is 1 to 1 to react at a temperature of 80 DEG C for 4 to 10 hours so as to obtain the target product. The duloxetine derivative prepared by the method has multiple mechanisms of action simultaneously, and can be used for preparing antidepressant drugs. Besides, the preparation process is simple and easy to operate.

Description

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Claims

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Application Information

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Owner HEBEI UNIV OF TECH
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