147770-06-7

Basic information

• Product Name: (+)-2-Ethoxy-4-(N-3-Methyl-1(S)-(2-(1-Piperidinyl)Phenyl)-Butyl)Carbamoylmethyl)
• Synonyms: (+)-2-Ethoxy-4-(N-3-Methyl-1(S)-(2-(1-Piperidinyl)Phenyl)-Butyl)Carbamoylmethyl);(+)-2-ETHOXY-4-(N-3-METHYL-1(S)-(2-(1-PEPERIDINYL)PHENYL)-BUTYL)CARBAMOYLMETHYL) BENZOIC ACID;(S)-Ethyl 2-ethoxy-4-[[[N-[1-(2-piperidinophenyl)-3-methyl-1-butyl]amino]carbonyl]methyl]benzoate;(S)-Repaglinide Ethyl Ether (Repaglinide Impurity);2-Ethoxy-4-[2-[[(1S)-3-methyl-1-[2-(1-piperidinyl)phenyl]butyl]amino]-2-oxoethyl]benzoic Acid Ethyl Ester;(S)-Repaglinide Ethyl Ester (Repaglinide Impurity);(S)-2-Ethoxy-4-[[[N-[1-(2-piperidinopheny;(S)-2-Ethoxy-4-[2-[[3-methyl-1-[2-(1-piperidinyl)phenyl]butyl]amino]-2-oxoethyl]-benzoicacid ethyl ester
• CAS NO: 147770-06-7
• Molecular Formula: C29H40N2O4
• Molecular Weight: 480.64
• Product Categories: Pharmaceutical material and intermeidates;Chiral Reagents;Impurities;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 147770-06-7.mol

Chemical Properties

• Melting Point: 115-118?C
• Boiling Point: 664.088°C at 760 mmHg
• Flash Point: 355.428°C
• Appearance: /
• Density: 1.093±0.06 g/cm3 (20 ºC 760 Torr)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.548
• Storage Temp.: -20°C Freezer
• Solubility: Chlorofrom, Methanol
• PKA: 14.79±0.46(Predicted)
• CAS DataBase Reference: (+)-2-Ethoxy-4-(N-3-Methyl-1(S)-(2-(1-Piperidinyl)Phenyl)-Butyl)Carbamoylmethyl)(CAS DataBase Reference)
• NIST Chemistry Reference: (+)-2-Ethoxy-4-(N-3-Methyl-1(S)-(2-(1-Piperidinyl)Phenyl)-Butyl)Carbamoylmethyl)(147770-06-7)
• EPA Substance Registry System: (+)-2-Ethoxy-4-(N-3-Methyl-1(S)-(2-(1-Piperidinyl)Phenyl)-Butyl)Carbamoylmethyl)(147770-06-7)

Safety Data

• Hazardous Substances Data: 147770-06-7(Hazardous Substances Data)

Usage

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 147770-06-7 differently. You can refer to the following data:
1. Repaglinide impurity.
2. Repaglinide impurity

InChI:InChI=1/C29H40N2O4/c1-5-34-27-19-22(14-15-24(27)29(33)35-6-2)20-28(32)30-25(18-21(3)4)23-12-8-9-13-26(23)31-16-10-7-11-17-31/h8-9,12-15,19,21,25H,5-7,10-11,16-18,20H2,1-4H3,(H,30,32)/t25-/m0/s1

Upstream product

• 99469-99-5 2-(3-ethoxy-4-(ethoxycarbonyl)phenyl) acetic acid 
• 147769-93-5 (1S)-3-methyl-1-(2-piperidin-1-ylphenyl)butan-1-amine 
• 108175-51-5 ethyl 2-ethoxy-4-<2-<<3-methyl-1-<2-(1-piperidinyl)phenyl>butyl>amino>-2-oxoethyl>-benzoate 
• 110-89-4 piperidine 
• 72752-52-4 2-(piperidin-1-yl)benzonitrile 
• 873-32-5 2-Chlorobenzonitrile 
• 108157-52-4 (S)-1-(2-piperidino-phenyl)-3-methyl-1-butylamine 
• 147769-96-8 3-methyl-1-[2-(piperidin-1-yl)phenyl]butan-1-imine 
• 50-85-1 2-hydroxy-p-toluic acid 
• 88709-17-5 ethyl 2-ethoxy-4-methyl-benzoate 
• 34595-26-1 2-(piperidin-1-yl)benzaldehyde 
• 110017-07-7 ethyl 4-bromomethyl-2-ethoxy-benzoate 
• 1026508-90-6 [3-Methyl-1-(2-piperidin-1-yl-phenyl)-but-3-enyl]-[1-(2-piperidin-1-yl-phenyl)-meth-(E)-ylidene]-amine 
• 147770-07-8 ethyl (S)-2-hydroxy-4-[N-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-aminocarbonylmethyl]-benzoate 

Downstream Products

• 135062-02-1 (S)-repaglinide 

Relevant articles and documents

Synthesis process of hypoglycemic drug repaglinide

The invention discloses a synthesis process of a hypoglycemic drug repaglinide. The process comprises the following steps: a) by using a compound II (S,S')-3-methyl-1-(2-piperidinophenyl)butylamine asa raw material, dissociating with an alkali, and directly condensing the obtained organic phase containing a compound III repigine with a compound IV 3-ethoxy-4-ethoxycarbonyl phenylacetic acid in the presence of an acylation reagent and an alkali without concentration; b) refining the compound V repaglinide ester crude product obtained after condensation by using an alkane solvent; and c) hydrolyzing in the presence of an alcohol solvent and an inorganic alkali, carrying out acidifying of post-treatment at a proper temperature, and purifying the obtained compound I repaglinide crude productby using an alcohol-water mixed solvent to obtain a repaglinide fine product. The synthesis process provided by the invention simplifies the synthesis steps, has the advantages of environmental protection, simple operation, high yield, low cost and the like, and is a repaglinide synthesis process suitable for industrial large-scale production.

Synthesis method of repaglinide

The invention discloses a synthesis method of repaglinide, and belongs to the technical field of medicine synthesis. The method comprises the following steps that ortho-halogenated benzaldehyde is taken as a raw material, a 2-piperidine-1-benzaldehyde compound 1 is obtained through piperidine substitution and reacts with (R)-methylpropane-2-sulfinamide to obtain an imine compound 2, then the iminecompound 2 reacts with a 2-methyl-1-propylene Grignard reagent lithium chloride, and through reduction, an S-(+)-1-(2-piperidine phenyl)-3-methyl n-butylamine compound 3 is obtained; then the S-(+)-1-(2-piperidine phenyl)-3-methyl n-butylamine compound 3 and 4-carboxyl methyl-2-ethoxy benzoate are condensed to obtain an S-(+)-2-oxethyl-4-[N-{1-(2-piperidine phenyl)-3-methyl-1-butyl}amine carbonylmethyl]benzoate compound 4; finally, the repaglinide 5 is obtained through hydrolysis. Compared with other technologies, the synthesis method has the advantages that operation is simple, the raw materials are easy to obtain, the yield is high, the cost is low, and the method is environmentally friendly; the product repaglinide has very high optical purity and is suitable for industrial production.

Studies on diastereofacial selectivity of a chiral tert-butanesulfinimines for the preparation of (S)-3-Methyl-1-(2-piperidin-1-yl-phenyl)butylamine for the synthesis of repaglinide

A new method for the asymmetric synthesis of a series of chiral amines including (S)-3-methyl-1-(2-piperidin-1-yl-phenyl)butylamine (2a) a key intermediate to prepare antidiabetic drug repaglinide by using Ellman's reagent tert-butanesulfinamide. Diastereoselective addition of organometallic reagents to t-butanesulfinimines and followed by acidic and basic treatment. The obtained chiral amines were characterized by NMR, MS and other analytical data.

Process for the preparation of substantially optically pure Repaglinide and precursors thereof

The invention relates to a process for preparing substantially optically pure Repaglinide and pharmaceutically acceptable salts, solvates and esters thereof, as well as precursors therefore.

Repaglinide Substantially Free of Dimer Impurity

The present invention provides highly pure repaglinide substantially free of dimer impurity, and process for the preparation thereof. The present invention also relates to 2-ethoxy-N-[(1S)-3-methyl-1-[2-(1-piperidinyl)phenyl]butyl]-4-[2-[[(1S)-3-methyl-1-[2-(1-piperidinyl)phenyl]butyl]amino]-2-oxoethyl]benzamide, an impurity of repaglinide, and a process for preparing and isolating thereof. The present invention further relates to pharmaceutical compositions comprising solid particles of pure repaglinide substantially free of dimer impurity or pharmaceutically acceptable salts thereof, wherein 90 volume-percent of the particles (D90) have a size of less than about 400 microns. The present invention also provides an optical resolution method of racemic 3-methyl-1-(2-piperidino-phenyl)-1-butylamine and use thereof for the preparation of repaglinide.

Process for preparing (alphaS)-alpha-(2-methylpropyl)-2-(1-piperidinyl)benzenemethanamine

The present invention relates to a process for the preparation of (αS)-α-(2-methylpropyl)-2- (1-piperidinyl)benzenemethanamine of Formula I, which is a key intermediate for the synthesis of Repaglinide.

Process for Preparing Ethyl (s)-2-Ethoxy-4-[N-[1-(2-Piperidinophenyl)-3-Methyl-1-Butyl]Aminocarbonyl Methyl]Benzoate and Use Thereof for the Preparation of Repaglinide

Described herein is an improved, commercially viable and industrially advantageous process for the preparation of Repaglinide intermediate, ethyl (S)-2-ethoxy-4-[N-(1-(2-piperidino-phenyl)-3-methyl-1-butyl)-aminocarbonylmethyl]-benzoate. The process provides the Repaglinide intermediate in higher yield and purity compared to the previously disclosed processes, thereby providing for production of Repaglinide and its pharmaceutically acceptable salts in high purity and in high yield.

An improved process for repaglinide via an efficient and one pot process of (1S)-3-methyl-1-(2-piperidin-1-ylphenyl)butan-1-amine - A useful intermediate

The development of a large-scale synthesis for (1S)-3-methyl-1-(2- piperidin-1-ylphenyl)butan-1-amine (S-(+)-1), a key intermediate of repaglinide (2), is described. The process conditions for S-(+)-1 involving nucleophilic substitution, Grignard reaction, reduction and resolution were optimized and telescoped. The racemization of the undesired enantiomer R-(-)-1 offers a distinctive advantage in terms of cost and overall yield over the existing process. This communication also describes the control of a DCU byproduct obtained during the condensation of S-(+)-1 with phenyl acetic acid derivative 3 in the synthesis of 2. Schweizerische Chemische Gesellschaft.

PROCESS FOR THE PREPARATION OF S(+)-2-ETHOXY-4-[N-{1-(2-PIPERIDINOPHELYL)-3-METHYL-1- BUTYL} AMINOCARBONYLMETHYL]BENZOIC ACID DERIVATIVES

The present invention relates to a novel process for the preparation of S(+)-2-ethoxy-4-[N-{1-(2-piperidinophelyl)-3-methyl-1-butyl} aminocarbonylmethyl]-benzoic acid derivatives.

METHOD FOR THE PRODUCTION OF PHENYLACETIC ACID DERIVATIVES

Disclosed is a method for producing (S) (+) phenylacetic acid derivatives of general formula (I), wherein R1 represents a linear or branched alkyl radical with 1 to 6 carbon atoms or optionally substituted benzyl while R2 represents methyl, ethyl, or propyl. The inventive method is characterized in that a compound of general formula (II), wherein R1 has the meaning indicated above and R3 represents a nucleofuge, or a suitable salt of a compound of general formula (II) is reacted with a compound of general formula (III), wherein R2 has the meaning indicated above and R4 represents hydrogen or a hydrolytically cleavable nucleofuge, whereupon the optionally provided protective group R4 is eliminated.