- METHODS FOR PREPARING CILOSTAZOL AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
-
The present invention relates to a method for preparing cilostazol and a pharmaceutical formulation comprising the same. A method for preparing crystalline A cilostazol and a cilostazol pharmaceutical preparation manufactured by using the same are provided. The cilostazol prepared according to the method of the present invention has high yield, has high purity, has a low impurity content, and has less side effects and excellent emission characteristics. A method for preparing cilostazol according to the present invention is characterized by having less environmental pollution compared to the conventional method using a single catalyst. (by machine translation)
- -
-
Paragraph 0101-0139; 0145
(2020/10/22)
-
- A preparation of cilostazol (by machine translation)
-
The invention discloses a method for preparation of cilostazol, to the nitro - 3 - bromophenol and 1 - cyclohexyl - 5 - (4 - chlorobutyl) - 1 H - tetrazole as raw materials, the inorganic alkali under the action of reaction to obtain the compound (1); compound (1) reduction to obtain compound (2); compound (2) in the presence of allyl chloride acid and reaction to obtain compound (3); compound (3) in the catalyst catalyzes the cyclization to obtain cillo he azole. The present invention uses the chain 1 - cyclohexyl - 5 - (4 - chlorobutyl) - 1 H - tetrazole as phenolic hydroxyl protecting group, thereby reducing the cilostazol of synthetic steps, and the cost is saved, and improves the yield; and to avoid the use of strong corrosion of the aluminum, so that the reaction is more moderate, easy operation, and less environmental pollution, is suitable for industrial production, to the health of the operating personnel are more secured. At the same time reduced in the product more difficult to remove the potential gene toxic impurities in the product of the residual risk. (by machine translation)
- -
-
-
- Preparation method of cilostazol
-
The invention discloses a preparation method of cilostazol and belongs to the field of medicines. The preparation method comprises the following steps: firstly, reacting 4-methoxyaniline with 3-chloropropionyl chloride in the presence of a solvent or no solvent; after a TLC (thin layer chromatography) detecting reaction is finished, adding aluminum trichloride into a system, and carrying out temperature raising reaction for 1 to 16 hours to obtain 6-hydroxy-3,4-dihydroquinoline-2-keto; secondly, in the presence of alkali, carrying out heating reaction on the 6-hydroxy-3,4-dihydroquinoline-2-keto obtained in the first step and 5-(4-chlorobutyl)-1-cyclohexanyl tetrazole in normal propyl alcohol to obtain the cilostazol. The high-purity cilostazol can be obtained by adopting the method disclosed by the invention; the preparation method has the advantages of few steps of the whole synthetic route, high yield, low cost, less wastewater and suitability for industrial production.
- -
-
-
- Synthetic method of cilostazol
-
The invention discloses a synthetic method for cilostazol. In an alcohol-water system, inorganic alkali is taken as a catalyst, and quinolone derivatives and tetrazole derivatives react at the temperature of 75 to 80 DEG C to generate cilostazol. According to the invention, the alcohol-water mixed system is taken as a reaction medium, the reaction process is a homogeneous system, and the liquid expansion does not occur, and foam is not filled with a kettle. Furthermore, after the reaction is completed, a lower-layer alkaline containing water phase can be separated via standing still, and an upper-layer organic phase is cooled and crystallized to achieve the purification effect. The purity of the product can reach 99.6% or higher.
- -
-
Paragraph 0023; 0024; 0029; 0030; 0031; 0032; 0033-0040
(2017/12/27)
-
- Convergent Three-Component Tetrazole Synthesis
-
A microwave-accelerated, simple, and efficient method for the construction of the 1,5-tetrazole scaffold was developed. It comprises a multicomponent reaction of an amine, a carboxylic acid derivative, and an azide source. On the basis of the availability of the archetypical starting materials, this method provided very versatile synthetic access to 1,5-disubstituted tetrazoles. The usefulness of this method was demonstrated in the synthesis of biologically important fused tetrazole scaffolds and the marketed drug cilostazol.
- Chandgude, Ajay L.,D?mling, Alexander
-
supporting information
p. 2383 - 2387
(2016/06/01)
-
- Synthesis of related substances of cilostazol
-
The impurities in API of cilostazol were detected by LC/MS during the process development. The structures of two impurities 6 and 7 and the related formation mechanisms were proposed. Synthesis of 6 and 7 was conducted for confirmation of the speculated structures.
- Zheng, Jin,Liu, Zheng,Dai, Yiru,Zhao, Qingjie,Shen, Jingshan
-
scheme or table
p. 189 - 195
(2009/05/07)
-
- Process for the production of cilostazol
-
A process for the preparation of cilostazol of formula I from 6-hydroxy-3,4-dihydroquinolinone of formula II and 1-cyclohexyl-5-(4-halobutyl)-tetrazole of formula III, wherein X is a halogen atom such as Cl, Br, and I, that includes combining compounds II, III, a water-miscible organic solvent, a water-soluble base and water. The cilostazol can then be separated from the reaction mixture and dissolved in a solvent A. The resulting cilostazol solution is mixed with a solvent B to precipitate cilostazol particles of defined particle size range, milling the precipitate if desired, and filtering and drying the product.
- -
-
Page/Page column 3-4
(2008/06/13)
-
- PROCESS FOR PURIFICATION OF CILOSTAZOL
-
The present invention provides a process for preparing high purity cilostazol. The process comprises: (a) adding crude cilostazol to an acid selected from the group consisting of oxalic acid, maleic acid, sulfuric acid, and a mixture thereof to form a cilostazol salt; and (b) recovering cilostazol through adding a base to the cilostazol salt.
- -
-
Page/Page column 3
(2008/06/13)
-
- Highly pure cilostazol and an improved process for obtaining same
-
A novel process for preparing highly pure cilostazol, effected by reacting 6-hydroxy-3,4-dihydroquinolinone and 5-(4-chlorobutyl)-1-cyclohexyl-1H-tetrazole in the presence of a hydrated inorganic base, is disclosed. Further disclosed is highly pure cilostazol, and particularly highly pure cilostazol that is substantially free of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-1-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butyl]-3,4-dihydro-1H-quinolin-2-one.
- -
-
Page/Page column 5; 9
(2008/06/13)
-
- Substantially pure cilostazol and processing for making same
-
The present invention provides substantially pure cilostazol. The present invention also provides cilostazol particles that have reduced particle size.
- -
-
-
- Substantially pure cilostazol and processes for making same
-
The present invention provides substantially pure cilostazol. The present invention also provides cilostazol particles that have reduced particle size.
- -
-
-
- PROCESS FOR PRODUCING CILOSTAZOL
-
The present invention provides a process for producing cilostazol [I] in a high yield and a high purity, by reacting a carbostyril derivative [II] with a tetrazole derivative [III] in the presence of an inorganic basic compound in a solvent of water, wherein water is used in an amount of 3 to 7-fold weight to that of the carbostyril derivative [II] and the inorganic basic compound is used in an amount of 1 to 6 mol per mol of the carbostyril derivative [II]. The process of the present invention is the improved and environment-friendly process for producing cilostazol being useful for pharmaceuticals.
- -
-
-
- Process for producing carbostyril derivatives
-
The present invention provides a process for producing carbostyril derivatives (I) which are known to be useful as medical drug such as antithrombotic agent, cerebral circulation improver, anti-inflammatory agent, antiulcer agent, etc. in a high yield and a high purity. The carbostyril derivatives (I) can be produced by reacting a carbostyril derivative (II) with a tetrazole derivative (III) in the presence of a phase transfer catalyst.
- -
-
-
- Substantially pure cilostazol and processes for making same
-
The present invention provides substantially pure cilostazol. The present invention also provides cilostazol particles that have reduced particle size.
- -
-
-
- Process for producing carbostyril derivatives
-
The present invention provides a process for producing carbostyril derivatives (I) which are known to be useful as medical drug such as antithrombotic agent, cerebral circulation improver, anti-inflammatory agent, antiulcer agent, etc. in a high yield and a high purity. The carbostyril derivatives (I) can be produced by reacting a carbostyril derivative (II) with a tetrazole derivative (III) in the presence of a phase transfer catalyst.
- -
-
-
- Process for producing carbostyril derivatives
-
The present invention provides a process for producing carbostyril derivatives (I) which are known to be useful as medical drug such as antithrombotic agent, cerebral circulation improver, anti-inflammatory agent, antiulcer agent, etc. in a high yield and a high purity. The carbostyril derivatives (I) can be produced by reacting a carbostyril derivative (II) with a tetrazole derivative (III) in the presence of a phase transfer catalyst.
- -
-
-
- Studies on 2-oxoquinoline derivatives as blood platelet aggregation inhibitors. II. 6-[3-(1-Cyclohexyl-5-tetrazolyl)propoxy]-1,2-dihydro-2-oxoquinoline and related compounds
-
A series of ω-(1-substituted-5-tetrazolylalkoxy)-2-oxoquinolines was synthesized and tested for inhibitory activity towards collagen- and adenosine diphosphate (ADP)-induced aggregation of rabbit blood platelets in vitro. These compounds were prepared by the reaction of 1-substituted-5-(ω-chloroalkyl)-tetrazoles and hydroxy-2-oxoquinolines in the presence of a base. Among them, 6-[3-(1-cyclohexyl-5-tetrazolyl)propoxy]-1,2-dihydro-2-oxoquinoline (IVb) was found to have the most potent inhibitory activity. The structure-activity relationships are discussed.
- Nishi,Tabusa,Tanaka,Shimizu,Kanbe,Kimura,Nakagawa
-
p. 1151 - 1157
(2007/10/02)
-
- TETRAZOLYLALKOXYCARBOSTYRIL DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
-
Novel tetrazolylalkoxycarbostyril derivative of the formula (I).The above-mentioned novel tetrazolylalkoxycarbostyril derivatives have pharmacological activities such as platelet aggregation inhibitory action, antiinflammatory action, antiulcer action, vasodilatory action and phosphodiesterase inhibitory action and are useful as anti-thrombosis agent, cerebral blood flow improving agent, antiinflammatory agent, antiulcer agent, anti-hypertensive agent and anti-asthmatic agent
- -
-
-