763114-26-7Relevant articles and documents
Novel preparation method of olaparib
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, (2021/08/11)
The invention relates to a novel preparation method of olaparib. The novel preparation method comprises the following preparation steps: 1, reacting 4-methylphthalazin-1(2H)-one with NBS and AIBN in a reaction solvent; 2, carrying out a coupling reaction on 4-(bromomethyl)phthalazin-1(2H)-one and (4-fluoro-3-(methoxycarbonyl)phenyl)boric acid in a reaction solvent under the action of a catalyst and an alkali; 3, hydrolyzing methyl 2-fluoro-5-((4-oxo-3, 4-phthalazin-1-yl)methyl)benzoate in a reaction solvent under the action of alkali; and 4, reacting the 2-fluoro-5-((4-oxo-3, 4-dihydrophthalazin-1-yl)methyl)benzoic acid with cyclopropyl (piperazine-1-yl)methyl ketone hydrochloride in a reaction solvent under the action of a condensing agent and alkali to obtain a crude olaparib product, and recrystallizing to obtain the high-purity olaparib. According to the process of the novel preparation method, the total yield can be effectively improved, impurities caused by cyano hydrolysis can be obviously reduced, and the purity and quality of the prepared olaparib are improved.
Preparation method of 2-fluoro-5-[(4-oxo-3H-2,3-diazanaphthalene)methyl]benzoic acid
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Paragraph 0005; 0012, (2021/04/10)
The invention discloses a preparation method of 2-fluoro-5-[(4-oxo-3H-2,3-diazanaphthalene)methyl]benzoic acid, wherein the method comprises the steps: S1, preparation of (3-oxo-1,3-dihydroisobenzofuran-1-yl)dimethyl phosphate; S2, preparation of 2-fluoro-5-(3-oxo-3H-isobenzofuran-1-yl methylene)bromobenzene; S3, preparation of 2-fluoro-5-(3-oxo-3H-isobenzofuran-1-yl methylene)methyl benzoate; and S4, preparation of 2-fluoro-5-[(4-oxo-3H-2,3-diazanaphthalene)methyl]benzoic acid. The preparation method has the advantages of simple operation, mild reaction conditions, easy purification of the intermediates, increase of the total yield compared with the prior art, and reduction of the industrial cost.
Olaparib intermediate and preparation method of olaparib
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Paragraph 0015; 0028; 0031-0032; 0035; 0038-0039; 0042; 0045, (2021/03/18)
The invention discloses an olaparib intermediate and a preparation method of olaparib, and the method comprises the following steps: suspending a compound II in a solvent, adding alkali, heating to areaction temperature, and reacting to obtain a compound III; mixing the compound III with a solvent, adding hydrazine hydrate and alkali, heating to a reaction temperature, and keeping the temperatureto react to a reaction end point to obtain a compound IV; and mixing and stirring the compound IV, a catalyst and a solvent, heating to a reaction temperature, adding thionyl chloride, carrying out aheat preservation reaction to the reaction end point, cooling, sequentially adding an alkali and cyclopropanoyl piperazine, carrying out a heat preservation reaction until the reaction is complete, and reacting to obtain olaparib according to a reaction formula shown in the specification. The method provided by the invention has the advantages of cheap and easily available raw materials, simple operation, mild reaction conditions, high purity and high yield of the obtained target product, no highly toxic substances, simple post-treatment and less three wastes, and meets the green and environment-friendly production requirements.