Novel method for synthesizing tiropramide hydrochloride

A technology of tiromide hydrochloride and a new method, which is applied in the field of synthesizing tiromide hydrochloride, can solve the problems of high cost, low yield, and low purity, and achieve the effects of simple and mild reaction, improved economic benefits, and simplified post-treatment

Active Publication Date: 2017-12-01
上海常丰生物医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In order to solve the problems existing in the prior art, the present invention provides a new method for synthesizing tiromide hydrochloride, which can solve the problems of low yield, low purity and high cost of existing synthetic methods

Method used

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  • Novel method for synthesizing tiropramide hydrochloride
  • Novel method for synthesizing tiropramide hydrochloride
  • Novel method for synthesizing tiropramide hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Step 1: In a 5000ml four-necked reaction flask, add 2000ml of purified water, 110g of sodium carbonate, control the temperature to 10°C, add 100g of L-tyrosine, 100g of benzoyl chloride, control the temperature to 25°C, stir for 30min, drop Methanol 600ml, stirred for 1h, cooled to 5°C, and concentrated hydrochloric acid 700g was added dropwise. Stir for 1 h, centrifuge, wash with 300 ml of purified water, and dry the solid in vacuum at 80°C for 10 hours to obtain 210 g of dry O,N-2-benzoyl-L-tyrosine (content 99%).

[0029] Step 2: Add 1500ml of toluene into a 3000ml four-necked bottle, put in 100g of O,N-2-benzoyl-L-tyrosine and 90g of dipropylamine, heat up to reflux and divide water, react for 10h, and add the prepared concentrated hydrochloric acid 23g of dilute hydrochloric acid and 300g of purified water, stirred for 30min, separated into layers, and removed the water layer. Add 90g of sodium chloride and 300ml of purified water, stir for 30min, separate layers,...

Embodiment 2

[0032] Step 1: In a 5000ml four-necked reaction flask, add 2000ml of purified water, 143g of potassium carbonate, control the temperature to 10°C, add 100g of L-tyrosine, 100g of benzoyl chloride, control the temperature to 25°C, stir for 30min, drop Methanol 600ml, stirred for 1h, cooled to 5°C, and concentrated hydrochloric acid 700g was added dropwise. Stir for 1 h, centrifuge, wash with 300 ml of purified water, and dry the solid in vacuum at 80°C for 10 hours to obtain 203 g of dry O,N-2-benzoyl-L-tyrosine (content 99%).

[0033] Step 2: Add 1500ml of chlorobenzene into a 3000ml four-necked bottle, put in 100g of O,N-2-benzoyl-L-tyrosine and 90g of dipropylamine, heat up to reflux and divide water, react for 10h, add the prepared concentrated Dilute hydrochloric acid with 23 g of hydrochloric acid and 300 g of purified water was stirred for 30 min, separated into layers, and the water layer was removed. Add 90g of sodium chloride and 300ml of purified water, stir for 30m...

Embodiment 3

[0036] Step 1: In a 5000ml four-necked reaction flask, add 2000ml of purified water, 150g of sodium carbonate, control the temperature to 20°C, add 100g of L-tyrosine, 110g of benzoyl chloride, control the temperature to 30°C, stir for 30min, drop Methanol 600ml, stirred for 1h, cooled to 5°C, and concentrated hydrochloric acid 700g was added dropwise. Stir for 1 h, centrifuge, wash with 300 ml of purified water, and dry the solid in vacuum at 80°C for 10 hours to obtain 206 g of dry O,N-2-benzoyl-L-tyrosine (content 99%).

[0037] Step 2: Add 1500ml of toluene into a 3000ml four-necked bottle, put in 100g of O,N-2-benzoyl-L-tyrosine and 120g of dipropylamine, raise the temperature to reflux and divide water, react for 10 hours, and add the prepared concentrated hydrochloric acid 25g of dilute hydrochloric acid and 300g of purified water, stirred for 30min, separated into layers, and removed the water layer. Add 90g of sodium chloride and 300ml of purified water, stir for 30m...

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Abstract

The invention discloses a novel method for synthesizing tiropramide hydrochloride. The method comprises the following steps: 1, by taking L-tyrosine and benzoyl chloride as raw materials, performing an acylation reaction under the condition of an inorganic alkali water solution, and performing crystallization in alcohol water to obtain O,N-2-benzoyl-L-tyrosine; 2, by taking toluene as a solvent, adding the O,N-2-benzoyl-L-tyrosine and dipropyl amine, adding dilute hydrochloric acid and salt water, and removing the water layer to obtain N-benzoyl-L-tyrosyl di-n-propylamine; and 3, by taking an inorganic alkali water solution as a solvent and ethylenediamine tetraacetic acid as a catalyst, adding the N-benzoyl-L-tyrosyl di-n-propylamine and 2-diethylaminoethyl chloride hydrochloride to obtain the tiropramide hydrochloride. According to the novel method, new experimental conditions are used, the yield is increased, the purification problem of the product is solved, and the cost is lowered.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a new method for synthesizing tiromide hydrochloride. Background technique [0002] Mechanism of action of tiromide hydrochloride: to smooth muscle cells directly to antispasmodic, intracellular calcium ion antispasmodic effect to regulate the contraction of smooth muscle cells required for regulation of relaxation muscle contraction; the main effect is to act on acute spasmodic pain, hepatobiliary colic , abdominal cramps, renal, ureteral cramps, abdominal cramps and pain, increased gastrointestinal motility, cholelithiasis, cholecystitis and postoperative adhesions. [0003] At present, the synthesis method of tiromide hydrochloride is: use L-tyrosine and benzoyl chloride as raw materials to react under the condition of alkaline aqueous solution, crystallize in acetone water to obtain O,N-(2-benzoyl)-L-tyrosine Synthesis of O,N-(2-benzoyl)-L--tyrosine in ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C231/02C07C233/87C07C237/22C07C209/00C07C211/15C07C231/24
CPCC07C209/00C07C231/02C07C231/24C07C233/87C07C237/22C07C211/15
Inventor 张博王伟王东任永远顾盼
Owner 上海常丰生物医药科技有限公司
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