- Novel synthesis method of clevidipine butyrate important intermediate
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The invention discloses a preparation method of a clevidipine butyrate important intermediate. The preparation method comprises the steps that 3-Hydroxypropionitrile and diketene are condensed to obtain ethyl 2-cyanoacetoacetate (intermediate I); ethyl 2-cyanoacetoacetate, 2,3-dichlorobenzaldehyde and methyl 3-aminocrotonate are mixed, Hantzsch reaction is performed to obtain 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridine phthalate methyl ester-(2-cyano ethyl)-ester (intermediate II); the 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridine phthalate methyl ester-(2-cyano ethyl)-ester is hydrolyzed to obtain 4-(2,3- dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridine mono-Methyl phthalate, namely the clevidipine butyrate important intermediate. The intermediate involved in the synthesis process is not needed to be chromatographic separation and purification, the materials for synthesis are cheap and easy to obtain, the reaction speed is high, the conditions are mild, operation is simple and convenient, the process reliability is good, the yield is high, the purity of the obtained clevidipine butyrate important intermediate is above 99%, and the preparation method is suitable for mass production.
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Paragraph 0020
(2016/10/07)
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- Butyric acid clevidipine preparation method
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The invention discloses a preparation method of clevidipine butyrate, comprising the following steps: (1) carrying out one-pot reaction by putting 2,3-dichlorobenzaldehyde, methyl acetoacetate and 3-amino crotonic acid ethyl cyanide in a solvent under the action of a catalyst; (2) carrying out recrystallization to obtain a pure product (+/-)-3-(2-cyanoethyl)-5-methyl-4-(2',3'-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid; (3) carrying out a reaction between the pure product and alkali; (4) adding water and hydrochloric acid, and collecting an intermediate from reaction products; and (5) carrying out a reaction between the intermediate and n-chloromethyl butyrate in the presence of an alkaline substance and an iodide catalyst, and finally collecting the target product clevidipine butyrate from reaction products. The preparation method provided by the invention has advantages of high yield, stable product quality and low cost, is simple to operate, and is suitable for industrial product of clevidipine butyrate.
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Paragraph 0040; 0051-0052
(2017/01/17)
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- Mild and facile cleavage of 2-cyanoethyl ester using sodium sulfide or tetrabutylammonium fluoride. Synthesis of 1,4-dihydropyridine monocarboxylic acids and unsymmetrical 1,4-dihydropyridine dicarboxylates
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Several 3-(2-cyanoethyl)-1,4-dihydropyridine carboxylates (16) were prepared in moderate to good yields by means of the Hantzsch reaction. Treatment of these carboxylates with a weak base such as sodium sulfide or tetrabutylammonium fluoride at room temperature afforded smoothly the corresponding 1,4-dihydropyridine monocarboxylic acids (18) in good yields. The monocarboxylic acids 18n and 18o were esterified with 2-nitrooxypropanol or N-(2-hydroxyethyl)nicotinamide p-toluenesulfonic acid salt to afford the selective coronary vasodilators CD-349 (5) and CD-832 (6), respectively.
- Ogawa,Hatayama,Maeda,Kita
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p. 1579 - 1589
(2007/10/02)
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- Synthesis and antihypertensive activities of new 1,4-dihydropyridine derivatives containing a nitrooxy moiety at the 3-ester position
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The synthesis of a new series of dihydropyridines containing a nitrooxy moiety at the 3-ester position is described. The antihypertensive activity of the compounds was examined and compared with that of nifedipine; some of them were relatively potent. The structure-activity relationship is also discussed.
- Ogawa,Nakato,Tsuchida,Hatayama
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p. 108 - 116
(2007/10/02)
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