Preparation method of amiodarone hydrochloride key intermediate

A technology for amiodarone hydrochloride and intermediates, which is applied in the field of medicine, can solve the problems of increasing the cost of amiodarone hydrochloride, high processing costs, and cumbersome preparation, and achieves the effects of easy post-processing, less by-products, and simple route operations

Active Publication Date: 2021-11-02
SUZHOU HOMESUN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But, this route also has many problems: 1) the preparation of 2-butylbenzofuran (formula 1 compound) is very loaded down with trivial details, causes its price higher, also improves the cost of final product amiodaron

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  • Preparation method of amiodarone hydrochloride key intermediate
  • Preparation method of amiodarone hydrochloride key intermediate
  • Preparation method of amiodarone hydrochloride key intermediate

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preparation example Construction

[0029] The preparation method of the present invention can be expressed as follows:

[0030]

Embodiment 1

[0032] Dissolve benzofuranone 7 (20.1g, 150mmol) in dichloromethane (200mL), add triethylamine (35.4g, 350mmol), stir in ice bath (-10°C) for 30 minutes, then divide within half an hour Add p-methoxybenzoyl chloride (26.4g, 155mmol) in batches, and react in ice bath (-10°C) for 1 hour after the addition; then add valeryl chloride (19.9g, 165mmol) in batches, and react in ice bath after the addition Hour. After the reaction was completed, 100 mL of water was added to quench the reaction, the organic layer was separated, and washed successively with saturated sodium bicarbonate solution, water, and saturated brine, and the organic layer was evaporated to dryness to obtain compound 8, which was directly used in the next reaction; 1 HNMR (400MHz, CDCl 3 )δ7.82(d, J=7.6Hz, 2H), 7.52(d, J=8.0Hz, 1H), 7.39(m, 1H), 7.24(d, J=8.0Hz, 1H), 7.07(d, J=7.6Hz, 2H), 7.03(m, 1H), 3.85(s, 3H), 2.53(t, J=7.6Hz, 2H), 1.65–1.54(m, 2H), 1.43-1.32(m, 2H ),0.95(t,J=7.2Hz,3H).

[0033] Dissolve th...

Embodiment 2

[0035] Dissolve benzofuranone 7 (150mmol) in chloroform (200mL), add diisopropylethylamine (350mmol), stir in ice bath (0-10°C) for 30 minutes, then add p- After the addition of methoxybenzoyl chloride (155 mmol), react in an ice bath for 2 hours; then add valeryl chloride (165 mmol) in batches, and react in an ice bath (0-10° C.) for 2 hours after the addition. After the reaction was completed, 100 mL of water was added to quench the reaction, the organic layer was separated, and washed successively with saturated sodium bicarbonate solution, water, and saturated brine, and the organic layer was evaporated to dryness to obtain compound 8, which was directly used in the next reaction;

[0036] Dissolve the above compound 8 in xylene (270 mL), add sulfuric acid (15 mmol), and react under reflux (oil bath 150° C.) for 15 hours. After the reaction, the reaction solution was allowed to cool to room temperature, washed with 50 mL of water and 20 mL of saturated sodium bicarbonate s...

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Abstract

The invention discloses a preparation method of an amiodarone hydrochloride key intermediate. The method comprises the following steps: reacting benzofuranone with p-methoxybenzoyl chloride and valeryl chloride, and heating and reacting the product under an acidic condition to obtain the amiodarone hydrochloride key intermediate. According to the method, the key intermediate of amiodarone hydrochloride is prepared through a two-step simple reaction, the reaction condition is mild, byproducts are few, and aftertreatment is easy; due to the fact that aluminum trichloride is not used, no solid waste is generated; and the method has the advantages of simple route operation, high yield and lower cost than the existing route, and is very suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a preparation method of a key intermediate of amiodarone hydrochloride. Background technique [0002] Amiodarone hydrochloride (Amiodarone) is a class III antiarrhythmic drug widely used in the treatment and prevention of ventricular and supraventricular arrhythmias. Its α- and β-adrenoceptor blockade and mild I and IV antiarrhythmic drug properties, the curative effect on severe and fatal arrhythmia is very significant. In addition, amiodarone can also affect thyroxine metabolism. The toxicity of amiodarone is very small, the lethal dose of intravenous injection is 10 times of the therapeutic dose, and the lethal dose of oral administration is very large, so the toxicity can be ignored. Therefore, even long-term large doses of amiodarone are safe. This product is characterized by a long half-life, after being absorbed from the intestinal tract, the excretion is ve...

Claims

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Application Information

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IPC IPC(8): C07D307/80
CPCC07D307/80
Inventor 陆红彬樊超杨颖栋陆志丹
Owner SUZHOU HOMESUN PHARMA
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