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A kind of preparation method of amiodarone hydrochloride

A technology of amiodarone hydrochloride and compounds, which is applied in the field of medicine, can solve the problems of low yield and purity, and achieve the effects of high purity, simple process and low production cost

Active Publication Date: 2019-09-10
烟台万润药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0022] Aiming at the problems of low yield and low purity caused by the above-mentioned preparation of amiodarone hydrochloride, the present invention provides a method for amiodarone hydrochloride that is safe and environmentally friendly, has cheap and easy-to-obtain raw materials, simple process, low production cost, and high yield and purity. Preparation

Method used

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  • A kind of preparation method of amiodarone hydrochloride
  • A kind of preparation method of amiodarone hydrochloride
  • A kind of preparation method of amiodarone hydrochloride

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Experimental program
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Effect test

Embodiment 1

[0049] The synthesis of embodiment 1 amiodarone hydrochloride

[0050] Synthesis of compound shown in A, formula 3

[0051]

[0052] Add 276.7g (2.0mol) of anhydrous potassium carbonate, 97.6g (0.8mol) of 2-hydroxybenzaldehyde, 100g of N,N-dimethylformamide, and 300g of toluene into a 2L three-necked flask, stir mechanically, and set the temperature at 60-70°C 176.0g (0.84mol) alkyl 2-bromohexanoate was added dropwise at a temperature of 80-100°C, stirred and reacted for 2 hours, 320g of water was added, the water layer was separated, and the organic layer was washed with 320g of water Once, the solvent was evaporated at 0.09MPa / 80°C to obtain 190.2g of the compound represented by formula 3, with a GC purity of 98.8% and a yield of 95.0% (calculated as 2-hydroxybenzaldehyde).

[0053] Synthesis of compound shown in B, formula 4

[0054]

[0055] 200.4g (0.8mol) of the compound shown in formula 3 was added into 2L methanol solution dissolved with 93.4g (0.88mol) of trim...

Embodiment 2

[0079] The synthesis of embodiment 2 amiodarone hydrochloride

[0080] Synthesis of compound shown in A, formula 3

[0081]

[0082] Add 332.0g (2.4mol) of anhydrous potassium carbonate, 97.6g (0.8mol) of 2-hydroxybenzaldehyde, 130g of N,N-dimethylformamide, 600g of toluene into a 2L three-necked flask, stir mechanically, and set the temperature at 60-70°C 176.0g (0.84mol) alkyl 2-bromohexanoate was added dropwise at a temperature of 80-100°C, stirred and reacted for 2 hours, 400g of water was added, the water layer was separated, and the organic layer was washed with 400g of water Once, the solvent was evaporated at 0.09MPa / 80 to obtain 197.2g of the compound shown in formula 3, with a GC purity of 98.6% and a yield of 98.5% (calculated as 2-hydroxybenzaldehyde).

[0083] B, the synthesis of formula 4 compounds

[0084]

[0085] 200.4g (0.8mol) of the compound shown in formula 3 was added into 2L methanol solution dissolved with 127.2g (1.2mol) of trimethyl orthoforma...

Embodiment 3

[0109] The synthesis of embodiment 3 amiodarone hydrochloride

[0110] Synthesis of compound shown in A, formula 3

[0111]

[0112] Add 387.3g (2.8mol) of anhydrous potassium carbonate, 97.6g (0.8mol) of 2-hydroxybenzaldehyde, 140g of N,N-dimethylformamide, 600g of toluene into a 2L three-necked flask, stir mechanically, and set the temperature at 60-70°C 176.0g (0.84mol) alkyl 2-bromohexanoate was added dropwise at a temperature of 80-100°C, stirred and reacted for 2 hours, 500g of water was added, the water layer was separated, and the organic layer was washed with 500g of water Once, the solvent was evaporated at 0.09MPa / 80 to obtain 198.2g of the intermediate of formula 3 with a GC purity of 98.9% and a yield of 99.0% (calculated as 2-hydroxybenzaldehyde).

[0113] Synthesis of compound shown in B, formula 4

[0114]

[0115] 200.4g (0.8mol) of the compound shown in formula 3 was added into 2L methanol solution dissolved with 169.8g (1.6mol) of trimethyl orthoform...

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Abstract

The invention belongs to the field of medicine, and in particular relates to a preparation method of amiodarone hydrochloride. The method mainly uses 2-hydroxybenzaldehyde and 2-bromohexanoic acid alkyl ester as raw materials to prepare 2-butylbenzofuran, Using 2-butylbenzofuran as a raw material, amiodarone hydrochloride is prepared through Friedel-Crafts acylation, demethylation, iodization, etherification and salt formation. The method of the present invention has cheap and easy-to-obtain raw materials and simple process , high-purity, high-yield 2-butylbenzofuran and amiodarone hydrochloride can be obtained, the cost is low, the waste water is less, and it is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of medicine, in particular to a preparation method of amiodarone hydrochloride. Background technique [0002] Amiodarone, also known as amiodarone, was first synthesized by Marly Nitrogen and Chemical Products Company in Belgium and applied for production in West Germany in 1961. It was originally introduced as a coronary artery dilator. In the 1970s, Singh discovered its electrophysiological mechanism of action. In 1976, Rosenbam took the lead in applying it to the treatment of antiarrhythmia. Amiodarone hydrochloride is the hydrochloride salt of amiodarone, and its structural formula is as follows: [0003] [0004] 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 negligible. Therefore, even long-term use of larger doses is safe. Amiodarone is absorbed from the intestinal tract and excreted ver...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D307/80
Inventor 杜体建乔仁国肖景超杨光李炬马振堂乔磊易朝辉
Owner 烟台万润药业有限公司
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