145375-43-5

Basic information

• Product Name: [2(S)-cis]-Octahydro-gamma-oxo-alpha-(phenylmethyl)-2H-isoindole-2-butanoic acid
• Synonyms: MITIGLINIDE;Mitiglinide [inn];Unii-D86I0xlb13;(2S)-4-[(3aR,7aS)-octahydro-1H-isoindol-2-yl]-2-benzyl-4-oxobutanoic acid;[2(s)-cis]-octahydro-gamma-oxo-alpha-(phenylmethyl)-2h-isoindole-2-butanoic acid
• CAS NO: 145375-43-5
• Molecular Formula: C₁₉H₂₅NO₃
• Molecular Weight: 315.41
• EINECS: 1312995-182-4
• Mol File: 145375-43-5.mol

Chemical Properties

• Boiling Point: 519.6 °C at 760 mmHg
• Flash Point: 268 °C
• Appearance: /
• Density: 1.175
• Vapor Pressure: 1.27E-11mmHg at 25°C
• Refractive Index: 1.567
• PKA: 4.37±0.10(Predicted)
• CAS DataBase Reference: [2(S)-cis]-Octahydro-gamma-oxo-alpha-(phenylmethyl)-2H-isoindole-2-butanoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: [2(S)-cis]-Octahydro-gamma-oxo-alpha-(phenylmethyl)-2H-isoindole-2-butanoic acid(145375-43-5)
• EPA Substance Registry System: [2(S)-cis]-Octahydro-gamma-oxo-alpha-(phenylmethyl)-2H-isoindole-2-butanoic acid(145375-43-5)

Safety Data

• Hazardous Substances Data: 145375-43-5(Hazardous Substances Data)

Usage

Uses

Antineoplastic.

InChI:InChI=1/C19H25NO3/c21-18(20-12-15-8-4-5-9-16(15)13-20)11-17(19(22)23)10-14-6-2-1-3-7-14/h1-3,6-7,15-17H,4-5,8-13H2,(H,22,23)

Upstream product

• 145324-18-1 4-[(3aR,7aS)-octahydro-2H-isoindol-2-yl]-4-oxo-2-benzyl-butanoic acid 
• 197447-44-2 (S)-2-Benzyl-4-(3aR,7aS)-octahydro-isoindol-2-yl-4-oxo-butyric acid (S)-benzylcarbamoyl-phenyl-methyl ester 
• 204187-39-3 (S)-2-Benzyl-4-(3aR,7aS)-octahydro-isoindol-2-yl-4-oxo-butyric acid methyl ester 
• 1470-99-1 cis-hexahydroisoindoline 
• 865538-96-1 (S)-3-benzyldihydrofuran-2,5-dione 
• 3972-36-9 (2S)-benzylsuccinic acid 
• 1220913-25-6 (S)-3-benzyl-4-((3aR,7aS)-1H-isoindol-2(3H,3aH,4H,5H,6H,7H,7aH)-yl)-4-oxobutanoic acid 
• 2144-87-8 (cis)-2,3,3a,4,7,7a-hexahydro-1H-isoindole 
• 161829-92-1 (3aR,7aS)-octahydro-1H-isoindole hydrochloride 
• 204187-36-0 (S)-2-Benzyl-4-(3aR,7aS)-octahydro-isoindol-2-yl-4-oxo-butyric acid (1R,2S,6R,7S)-3,5-dioxo-4-aza-tricyclo[5.2.1.0^2,6]dec-8-en-4-yl ester 
• 5653-88-3 2-benzylidenesuccinic acid 
• 100-52-7 benzaldehyde 
• 1141896-00-5 (2S)-2-benzyl-1-((4R)-4-benzyl-2-oxo-oxazolidin-3-yl)-4-(cis-hexahydro-isoindolin-2-yl)-butane-1,4-dione 
• 125702-11-6 (E)-benzylidenesuccinic anhydride 

Relevant articles and documents

A kind of improved mitiglinide preparation method (by machine translation)

The invention relates to an improved mitiglinide preparation method, the method comprises the steps of (1): preparation of acyl chloride; step (2): active preparation of amides; step (3): 2 - (S)- benzyl - 4 - oxo - (cis - full hydrogenation isoindol - 2 - yl) butyric acid preparation; step (4): mitiglinide preparation, the process of the method is simple, high yield, low production cost, compared with the prior-anhydride method process, the purity of the product is obviously improved, easy to industrial production. (by machine translation)

Preparation method of mitiglinide calcium

The invention relates to a preparation method of mitiglinide calcium, which includes steps of step 1, synthesis of benzal butanedioic acid; step 2, synthesis of benzylsuccinic acid; step 3, synthesisof (S)-benzylsuccinic acid (R)-alpha- phenylethylamine; step 4, synthesis of (S)-benzylsuccinic acid; step 5, synthesis of 2S-dihydro-isoindole indolebutyric acid; step 6, synthesis of crude product of mitiglinide calcium; step 7, refining of mitiglinide calcium.

A kind of improved mitiglinide industrial preparation method

The invention provides an improved mitiglinide calcium (I) preparation method, and is characterized in that the preparation method successively comprises the steps: step 1, preparation of 2-benzyl succinic acid; step 2, preparation of (S)-2-benzyl succinic acid; step 3, preparation of 2-(S)-benzyl-4-oxo-(cis-perhydroisoindole-2-yl)butyric acid; and step 4, preparation of mitiglinide calcium. The invention provides the mitiglinide calcium industrialized preparation method having the advantages of being economical and practical, simple to operate, short in reaction period and high in yield.

Technology for synthesizing Mitiglinide intermediate

The invention relates to the field of pharmaceutical synthesis, in particular to a technology for synthesizing a Mitiglinide intermediate, namely 2-(s)-benzyl-4-oxo-(cis-octahydroisoindole-2-yl) benzyl butyrate. The synthesis technology comprises the steps that N,N'-carbonyldiimidazole and S-2-benzylsuccinic acid are sequentially added to ethyl acetate, cis-octahydroisoindole hydrochloride is added after reaction, then purified water is added, the pH value is adjusted by the addition of hydrochloric acid, the purified water is added to an ethyl acetate layer obtained after standing and liquid separation, the pH value is adjusted by the addition of a NaOH solution, ethyl acetate is added to a water layer obtained after standing and liquid separation, the pH value is adjusted by the addition of hydrochloric acid, standing and liquid separation are conducted and then the ethyl acetate layer is subjected to drying, filtering and washing; anhydrous potassium carbonate and benzyl bromide are sequentially added to the obtained ethyl acetate solution for reflux reacting, the purified water is added after cooling, standing and liquid separation are conducted, an organic layer is subjected to crystallization and further subjected to post-treatment to obtain a crude product of a target compound, and the target pure product is obtained after purification. By means of the synthesis technology, the high-content and high-purity Mitiglinide intermediate can be prepared.

Mitiglinide preparation method

The invention discloses a high purity mitiglinide calcium preparation method including the following steps: synthesis of (2S)-2-benzyl-3-(cis-hexahydro isoindole-2-carbonyl) propionic acid; synthesis of (2S)-2-benzyl-3-(cis-hexahydro isoindole-2-carbonyl) benzyl propionate; hydrolysis of the (2S)-2-benzyl-3-(cis-hexahydro isoindole-2-carbonyl) benzyl propionate; and synthesis of mitiglinide calcium. The method simplifies synthetic route, and has the characteristics of convenient operation, low cost of raw materials, low equipment requirement, economy, environmental protection and simple technology. According to the method, the (2S)-2-benzyl-3-(cis-hexahydro isoindole-2-carbonyl) propionic acid can be crystallized after esterification, and is easy for purification and preservation and easy for realization of industrialized production. Tests confirm that the preparation method is easy in postprocessing, good in reaction area selectivity, high in product purity and relatively low in cost, and is conducive to industrial production.

Mitiglinide calcium method for the preparation of

The invention provides a novel preparation method for Mitiglinide calcium hydrate. The method comprises the following steps: adopting cis-hexahydroisoindole as a raw material, conducting acylation reaction, hydrocarbonylation reaction, hydrolysis reaction

Novel mitiglinide calcium preparing method

The invention provides a novel mitiglinide calcium preparing method. According to the method, (S)-2-benzyl succinic acid is taken as the raw material, and deacidification is conducted to generate (S)-2-benzyl succinic anhydride; amidation is conducted between (S)-2-benzyl succinic anhydride and cis-hexahydroisoidolin to generate mitiglinide acid and an isomer byproduct; the isomer byproduct is separated out and subjected to isomerization to generate mitiglinide acid; acid-base salifying and salt exchange are conducted on the obtained mitiglinide acid to generate the product mitiglinide calcium. Compared with an existing anhydride-method technology, the method has the advantage that the purity of the product is improved remarkably. Compared with an active ester method and an amide method, the method has the advantages that the technology is simple, the yield is high, and production cost is low.

Method for the preparation of Mitiglinide Calcium Dihydrate

The present invention refers to a photomask, a proximity [...] dihydrate of provides manufacturing method. According to of the present invention manufacturing method, including imidazoles to solution chloride reclamation material-benzyl (S) blended solution high draw child factor pebble cis-same and a pumping process is carried out in direct response the hydrochloride salt a photomask, a proximity which includes directing an [...] dihydrate according to the voltage by rated excess, a photomask, a proximity-purity compound in a dihydrate [...] , prepared in high yield to be as well as safety the fabrication procedure relatively mild conditions, and the mass production method by using the mask pattern..

Identification, synthesis and characterization of impurities of (S)-Mitiglinide calcium dihydrate

(S)-Mitiglinide Calcium dihydrate (1), an important potent hypoglycemic agent. During laboratory optimization and later in bulk synthesis the formation of various impurities was observed. The method of preparation of most of these impurities is not availa

PROCESS FOR OBTAINING (S)-2-BENZYL-4-((3AR,7AS)-HEXAHYDRO-1 H-ISOINDOL- 2(3H)-YL)-4-OXOBUTANOIC ACID AND SALTS THEREOF

Comprising reacting compound (IV) with compound (V) in a solvent to give (S)-mitiglinide (II) and compound (III) as a by- product; removing the solvent and adding ethyl acetate to precipitate compound (III); collecting the solid and applying at least one cycle process comprising: - refluxing the solution of compound (III) with an organic solvent to give (S)-mitiglinide (II) and further compound (III) as a by-product, - removing the organic solvent and adding ethyl acetate to precipitate compound (III); and - separating the mother liquors from the solid, and mixing all the mother liquors; removing the ethyl acetate from the mother liquors to obtain (S)-mitiglinide.