89332-50-3

Upstream product

• 73963-42-5 1-cyclohexyl-5-(4-chlorobutyl)-1,2,3,4-tetrazole 
• 54197-66-9 3,4-dihydro-6-hydroxy-2(1H)-quinolinone 
• 104-94-9 4-methoxy-aniline 
• 5470-65-5 3-bromo-4-nitrophenol 
• 877303-63-4 cilostazol oxalate 
• 877303-65-6 cilostazol bisulfate 
• 877303-64-5 cilostazol malate 

Downstream Products

• 93632-84-9 OPC-13326 
• 87153-03-5 3,4-Dihydro-6-<4-<1-(cis-2-hydroxycyclohexyl)-1H-tetrazol-5-yl>butoxy>-2(1H)-quinolinone 
• 98360-32-8 3,4-Dihydro-6-<4-<1-(trans-3-hydroxycyclohexyl)-1H-tetrazol-5-yl>butoxy>-2(1H)-quinolinone 
• 98360-32-8 3,4-Dihydro-6-<4-<1-(cis-3-hydroxycyclohexyl)-1H-tetrazol-5-yl>butoxy>-2(1H)-quinolinone 
• 87153-04-6 OPC 13213 
• 87153-06-8 OPC 13217 
• 1266615-52-4 CLZ-DDQ 
• 1266615-51-3 CLZ-I₂ 

Relevant academic research and scientific papers

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)

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.

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.

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.

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.

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.

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.

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.