A kind of preparation method of high-purity milrinone

A technology of milrinone and sodium hydroxide, applied in the field of medicine, can solve the problems of relatively high reaction conditions, strict requirements on water for phenyllithium, unsuitable for industrial production, etc., and achieves high product purity, improved production environment, and hydrolysis. The effect of the process is simple and easy to operate
CN104387320BActive Publication Date: 2018-01-26HUZHOU ZHANWANG PHARMA
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
HUZHOU ZHANWANG PHARMA
Publication Date
2018-01-26

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Abstract

The invention discloses a preparation method for high-purity milrinone (shown as a formula (I), 1,6-dihydro-2-methyl-6-oxo-3,4-bipyridine-5-carbonitrile), and belongs to the field of chemical medicines. The method comprises: employing 4-methylpyridine as a raw material and acetylating with acetyl chloride, and hydrolyzing after the reaction is finished, so as to obtain a compound of a formula (III); mixing the compound of the formula (III) with glacial acetic acid, acetic anhydride and triethyl orthoformate, and reacting at 35 DEG C-45 DEG C, so as to obtain a compound of a formula (IV); performing cyclization on the compound of the formula (IV) and alpha-cyanoacetamide, so as to obtain a crude product of a compound of the formula (I); and refining the crude product of the formula (I) compound through an ethanol-water system, so as to obtain a high-purity refined product with the maximum interplanar spacing d of 8.39 + / - 0.02 Angstrom. The technology is relatively mild in reaction conditions and relatively simple in operation, and is capable of preparing the milrinone product with high purity and a single crystal form. The obtained milrinone crystal form is relatively excellent in solubility in normal saline or glucose, and is beneficial for improvement of the preparation quality.
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Description

technical field

[0001] The present invention relates to a preparation method of milrinone (1,6-dihydro-2-methyl-6-oxo-[3,4-bipyridine]-5-carbonitrile), specifically a The invention discloses a preparation method of high-purity single-crystal milrinone, which belongs to the technical field of medicine. Background technique

[0002] Milrinone (milrinone, formula I), the chemical name is 1,6-dihydro-2-methyl-6-oxo-[3,4-bipyridine]-5-carbonitrile, and the molecular formula is C 12 h 9 N 3 O, with a molecular weight of 211.22, is a white or off-white crystalline powder, and its structural formula is:

[0003]

[0004] Milrinone was first developed by the American Sterling company as an anti-heart failure drug. It was first approved by the FDA in the United States in 1987 and officially launched in the United States in 1992. It was subsequently marketed in the United Kingdom, France, Germany, the Netherlands, Belgium and other countries. .

[0005] Milrinone is a phosphodi...

Claims

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