- Preparation method of voriconazole intermediate
-
The invention is suitable for the technical field of chemical synthesis and medicine, and provides a preparation method of voriconazole intermediate, which comprises steps of: carrying out a bromination reaction on 4-chloro-6-ethyl-fluoropyrimidine, N-bromosuccinimide, azodiisobutyronitrile and a first solvent to obtain a first intermediate; carrying out condensation reaction on the first intermediate, 2',4'-difluoro-2-[1-(1H-1,2,4-triazolyl)]acetophenone, zinc powder subjected to acid treatment and a second solvent to obtain a second intermediate; mixing the second intermediate, a third solvent and potassium formate to obtain a mixed solution; and adding palladium carbon into the mixed solution, and carrying out reflux reaction in a protective atmosphere to obtain the voriconazole intermediate. According to the preparation method disclosed by the invention, the voriconazole intermediate with high yield and high purity can be prepared.
- -
-
Paragraph 0029-0031; 0035-0037; 0041-0043; 0047-0049; 0053
(2020/10/29)
-
- A 4 - (1-bromo-ethyl) - 5-fluoro-6-chloro-pyrimidine synthesis method
-
The invention discloses a method for synthesizing 4-(1-bromoethyl) -5-fluoro-6-chloropyrimidine. The synthesis method comprises the steps of reacting 2-fluoro-ethyl acetate which is inexpensive and readily available and is used as an initial material with propionyl chloride under basic conditions in a solvent to synthesize an intermediate product 2-fluoro propionyl ethyl acetate; then carrying out cyclization on 2-fluoro propionyl ethyl acetate and formamidine acetate as well as a base in a solvent to obtain a cyclized product; then chlorinating the cyclized product with a chlorinating reagent; and finally adding a brominating reagent and brominating the chlorinated product in the presence of an initiator to obtain 4-(1-bromoethyl) -5-fluoro-6-chloropyrimidine. The synthesis method disclosed by the invention has the advantages of simple process, available raw materials, high yield, safety and environmental protection, and is convenient to industrialize.
- -
-
-
- NOVEL COMPOUND HAVING ANGIOGENESIS INHIBITORY ACTIVITY, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
-
Disclosed are an anti-angiogenic compound, represented by Chemical Formula I, or a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutically acceptable composition including the same. Because the compound of Chemical Formular I potently suppresses the angiogenesis, the compound of Chemical Formula I is applicable to the prevention and treatment of diseases caused by aberrant activity of vascular endothelial growth factor, and available as an anti-angiogenic agent.
- -
-
Paragraph 0089; 0090
(2014/07/23)
-
- Novel Compound Having Angiogenesis Inhibitory Activity, Method for Preparing Same, and Pharmaceutical Composition Comprising Same
-
Disclosed are an anti-angiogenic compound, represented by Chemical Formula I, or a pharmaceutically acceptable salt thereof, a preparation method thereof, and a pharmaceutically acceptable composition including the same. Because the compound of Chemical Formula I potently suppresses the angiogenesis, the compound of Chemical Formula I is applicable to the prevention and treatment of diseases caused by aberrant activity of vascular endothelial growth factor, and available as an anti-angiogenic agent.
- -
-
Paragraph 0204; 0205
(2014/09/29)
-
- PROCESS FOR THE PREPARATION OF VORICONAZOLE AND INTERMEDIATES THEREOF
-
The present invention relates to an improved stereoselective process for the preparation of (2R,3S/2S,3R)-3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol intermediate compound. This intermediate compound is further used to prepare voriconazole—a triazole antifungal agent.
- -
-
Paragraph 0036; 0037
(2014/12/09)
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF VORICONAZOLE AND INTERMEDIATES THEREOF
-
The present invention relates to an improved stereoselective process for the preparation of (2R,3S/2S,3R)-3-(4-chloro-5-fluoropyrimidin-6-yl)-2-(2,4-difluorophenyl)- 1-(1H-l,2,4-triazol-1-yl)butan-2-ol intermediate compound. This intermediate compound is further used to prepare voriconazole - a triazole antifungal agent.
- -
-
Page/Page column 8
(2012/09/11)
-
- METALLO-OXIDOREDUCTASE INHIBITORS USING METAL BINDING MOIETIES IN COMBINATION WITH TARGETING MOIETIES
-
The presently disclosed subject matter is directed to metallo-oxidoreductase inhibitors having metal binding moities linked to a targeting moiety through a linking group or a direct bond, methods for screening for metallo-oxidoreductase inhibitors, and methods of treating an oxidoreductase related disorder by administering a metallo- oxidoreductase inhibitor to a subject in need of treatment thereof.
- -
-
Page/Page column 148
(2008/12/05)
-
- Preparation of triazoles by organometallic addition to ketones and intermediates therefor
-
A process for the preparation of a compound of the formula: or an acid addition or base salt thereof, wherein R is phenyl optionally substituted by 1 to 3 substituents each independently selected from halo and trifluoromethyl; R1 is C1-C6 alkyl; and “Het” is pyrimidinyl optionally substituted by 1 to 3 substituents each independently selected from C1-C4 alkyl, C1-C4 alkoxy, halo, oxo, benzyl and benzyloxy, comprising reacting a compound of the formula: with a compound of the formula wherein X is chloro, bromo or iodo, the reaction taking place in the presence of zinc; at least one of iodine or a Lewis acid; and an aprotic organic solvent: optionally further reacting the resulting compound with an acid or base to form the corresponding acid addition or base salt thereof.
- -
-
-
- Process development of voriconazole: A novel broad-spectrum triazole antifungal agent
-
In the synthesis of (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1H-1,2,4-triazol-1- yl)-2-butanol (voriconazole), the relative stereochemistry is set in the addition of a 4-(1-metalloethyl)-5-fluoropyrimidine derivative to 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)-1-ethanone. The diastereo-control of this reaction has been examined by variation of pyrimidine substitution pattern and by changes in the metalation and reaction conditions. Excellent diastereoselection (12: 1) is obtained using an organozinc derivative of 6-(1-bromoethyl)-4-chloro-5-fluoropyrimidine. After removal of the chlorine from the pyrimidine ring, the absolute stereochemistry of voriconazole is established via a diastereomeric salt resolution process using (1R)-10-camphorsulfonic acid. Synthetic routes to the pyrimidine partner have also been evaluated. The initial six-step development route from 5-fluorouracil has been superseded by a four-step synthesis involving fluorination of methyl 3-oxopentanoate and cyclisation with formamidine acetate.
- Butters, Mike,Ebbs, Julie,Green, Stuart P.,MacRae, Julie,Morland, Matthew C.,Murtiashaw, Charles W.,Pettman, Alan J.
-
-