Synthesis process of levosimendan

A compound, the technology of chloropropionyl chloride, which is applied in organic chemistry and other fields, can solve the problems of long synthetic route and harsh reaction conditions

Inactive Publication Date: 2015-10-21
QINGDAO AGRI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The synthetic route is relatively long, and there is an ammoniation reaction that requires the use of an autoclave, and the reaction conditions are relatively harsh

Method used

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  • Synthesis process of levosimendan
  • Synthesis process of levosimendan
  • Synthesis process of levosimendan

Examples

Experimental program
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Embodiment 1

[0023] Add acetanilide and aluminum trichloride in a molar ratio of 1:3 to a 1L flask in turn, add dichloromethane, the volume ratio of the mass of acetanilide to dichloromethane is 1:3, and stir to dissolve. Add 2-chloropropionyl chloride dropwise into the reactor, the molar ratio of 2-chloropropionyl chloride to acetanilide is 1.2:1, and the dropwise addition is completed within 1 hour. The reaction was incubated at 25°C for 3 hours, cooled, poured into ice water, filtered and washed with deionized water three times, and recrystallized from ethanol to obtain compound 1 with a yield of 84.2%.

[0024] Add metal sodium to a 1L flask, add ethanol, the mass ratio of the volume of ethanol to metal sodium is 40:1, slowly add diethyl malonate, diethyl malonate dropwise under ice bath cooling after the reaction is completed The molar ratio of ester to sodium metal is 1:2, the dropwise addition is completed within 1h, and the reaction is stirred for 2h. Compound 1 was added into the...

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Abstract

The invention provides a synthesis process of levosimendan. The process includes: taking acetanilide and 2-chloropropionylchloride as the starting materials, conducting Friedel-Crafts acylation to obtain N-[4-(2-chloropropionylchloride)phenyl]acetamide (compound 1), then synthesizing 6-(4-aminophenyl)-5-methyl-4, 5-dihydropyridazine-3(2H)-one (compound 2) by one-pot method, and further condensing the compound 2 with malononitrile to obtain levosimendan (compound 3). The process provided by the invention has the characteristics of few step, simple operation, easy separation and purification of product, high yield and low cost, and employs common chemical materials as the reagents, thus being a new process suitable for industrial production.

Description

technical field [0001] The present invention relates to a new process for preparing levosimendan. Background technique [0002] Levosimendan (Levosimendan) is the chemical name of compound 3 (R)-2-{[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl ) phenyl] hydrazino} malononitrile is a calcium sensitizer developed by Orion phama company in France. It was launched in Sweden for the first time in October 2000. The US FDA approved it to conduct Phase III clinical research in 2001. It was launched in the US in 2005 and registered in my country in 2010. It has been widely used in more than 30 countries in Europe and America. Compound 3, as a calcium sensitizer, improves cardiac function through a mechanism different from traditional inotropic drugs. It enhances myocardial contractility without increasing intracellular calcium concentration, heart rate and myocardial oxygen consumption, and dilates blood vessels , It is mainly used clinically to treat various acute heart fail...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D237/04
CPCC07D237/04
Inventor 孙云明董风英赵鑫
Owner QINGDAO AGRI UNIV
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