147769-93-5

Basic information

• Product Name: (S)-3-Methyl-1-(2-piperidin-1-ylphenyl)butylamine
• Synonyms: (S)-[A-(2-methylpropyl)-2-(1-piperidinyl)benzene-methanamine;(S)-3-METHYL-1-[2-(1-PIPERIDINYL)PHENYL]-BUTYLAMINE;Repaglinide Intermediate 1;Repaglinide intermediate 4;(S)-3-Methyl-1-(2-piperidin-1-ylphenyl)butylamine;Benzenemethanamine, .alpha.-(2-methylpropyl)-2-(1-piperidinyl)-, (.alpha.S)-;(S)-3-Methyl-1-(2-piperidine-1-yl-phenyl)-butylamine;(αS)-α-(2-Methylpropyl)-2-(1-piperidinyl)-benzenemethanamine
• CAS NO: 147769-93-5
• Molecular Formula: C16H26N2
• Molecular Weight: 246.39
• EINECS: 1312995-182-4
• Product Categories: Pharmaceutical material and intermeidates
• Mol File: 147769-93-5.mol

Chemical Properties

• Boiling Point: 370.5 °C at 760 mmHg
• Flash Point: 164.7 °C
• Appearance: /
• Density: 0.99 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.539
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• PKA: 10.20±0.10(Predicted)
• CAS DataBase Reference: (S)-3-Methyl-1-(2-piperidin-1-ylphenyl)butylamine(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-3-Methyl-1-(2-piperidin-1-ylphenyl)butylamine(147769-93-5)
• EPA Substance Registry System: (S)-3-Methyl-1-(2-piperidin-1-ylphenyl)butylamine(147769-93-5)

Safety Data

• Hazardous Substances Data: 147769-93-5(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3-MPBA is utilized as a chiral building block for the synthesis of various pharmaceuticals and organic compounds. Its ability to interact with neurotransmitter receptors makes it a valuable component in the development of new drugs targeting neurological disorders and mental health conditions.
Used in Drug Development for Neurological Disorders:
3-MPBA is employed as a potential candidate for the development of new drugs due to its interaction with neurotransmitter receptors in the brain. This property allows it to be explored for the treatment of neurological disorders and mental health conditions, offering a promising avenue for therapeutic intervention.
Used in Organic Chemistry Research:
As an organic compound, 3-MPBA is also used in various research applications within the field of organic chemistry. Its unique structure and properties make it a valuable tool for studying chemical reactions and mechanisms, contributing to the advancement of scientific knowledge in this area.

InChI:InChI=1/C16H26N2/c1-13(2)12-15(17)14-8-4-5-9-16(14)18-10-6-3-7-11-18/h4-5,8-9,13,15H,3,6-7,10-12,17H2,1-2H3/t15-/m0/s1

Upstream product

• 110-89-4 piperidine 
• 147769-96-8 3-methyl-1-[2-(piperidin-1-yl)phenyl]butan-1-imine 
• 873-32-5 2-Chlorobenzonitrile 
• 147769-98-0 N-acetyl-N-<(S)-3-methyl-1-(2-(1-piperidinyl)phenyl)-1-butyl>-amine 
• 108157-52-4 (S)-1-(2-piperidino-phenyl)-3-methyl-1-butylamine 
• 1098066-89-7 (S)-3-methyl-1-(2-piperidino-phenyl)-1-butylamine di-p-toluoyl-D-tartaric acid salt 
• 82212-00-8 1-(2-bromophenyl)piperidine 
• 590-86-3 isovaleraldehyde 
• 799255-58-6 C₂₃H₃₂N₂ 
• 6630-33-7 ortho-bromobenzaldehyde 
• 446-52-6 2-Fluorobenzaldehyde 
• 89-98-5 2-chloro-benzaldehyde 

Downstream Products

• 147770-06-7 (S)-(+)-ethyl 2-ethoxy-4-<2-<<3-methyl-1-<2-(1-piperidinyl)phenyl>butyl>amino>-2-oxoethyl>-benzoate 
• 147769-98-0 N-acetyl-N-<(S)-3-methyl-1-(2-(1-piperidinyl)phenyl)-1-butyl>-amine 
• 135062-02-1 (S)-repaglinide 
• 1098066-88-6 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 
• 147770-08-9 (R)-(-)-ethyl 2-ethoxy-4-<2-<<3-methyl-1-<2-(1-piperidinyl)phenyl>butyl>amino>-2-oxoethyl>-benzoate 
• 219921-93-4 (R)-3-methyl-1-(2-(1-pieridinyl)phenyl)-butylamine 

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.

Preparation method for (S)-(+)-1-(2-piperidine phenyl)-3-methyl n-butylamine

The invention provides a preparation method for (S)-(+)-1-(2-piperidine phenyl)-3-methyl n-butylamine. The method comprises process steps as described in the specification. According to the invention, the (S)-(+)-1-(2-piperidine phenyl)-3-methyl n-butylamine is synthesized with 3-methyl-1-(2-piperidine phenyl)-1-butanone as a raw material by using a catalytic asymmetric synthetic method. The synthetic method provided by the invention has the advantages of easily-available raw materials, short synthetic route and high yield.

Reversal diastereoselectivity between the organomagnesium and organolithium reagents on Chiral N-tert-butylsulfinylaldimines for the preparation of chiral amines

The asymmetric synthesis of both the enantiomer of chiral amines from the single chiral source of N-tert-butylsulfinylaldimines (3) by simply changing the organometallic reagents through diastereoselective addition. An efficient enantioselective synthesis of chiral amines including (S)-3-methyl-1-(2- piperidin-1-yl-phenyl)butyl amine (6a), a key intermediate to prepare antidiabetic drug repaglinide (1), is reported.

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.

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 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.

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.

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.

Repaglinide and related hypoglycemic benzoic acid derivatives

The structure-activity relationships in two series of hypoglycemic benzoic acid derivatives (5, 6) were investigated. Series 5 resulted from meglitinide (3) when the 2-methoxy was replaced by an alkyleneimino residue. Maximum activity was observed with the cis-3,5-dimethylpiperidino (5h) and the octamethyleneimino (5l) residues. Series 6 resulted from the meglitinide analogon 4 bearing an inversed amido function when the 2-methoxy, the 5- fluoro, and the α-methyl residue were replaced by a 2-piperidino, a 5- hydrogen, and a larger α-alkyl residue, respectively. An alkoxy residue ortho to the carboxy group further increased activity and duration of action in the rat. The most active racemic compound, 6al (R4 = isobutyl; R = ethoxy), turned out to be 12 times more active than the sulfonylurea (SU) glibenclamide (1). Activity was found to reside predominantly in the (S)- enantiomers. Compared with the SUs 1 and 2 (glimepiride), the most active enantiomer, (S)-6al (AG-EE 623 ZW; repaglinide; ED50 = 10 μg/kg po), is 25 and 18 times more active. Repaglinide turned out to be a useful therapeutic for type 2 diabetic patients; approval was granted recently by the FDA and the EMEA. From investigations on the pharmacophoric groups in compounds of type 5 and 6, it was concluded that in addition to the two already known - the acidic group (COOH; S02NH) and the amidic spacer (CONH; NHCO) - the ortho residue R1 (alkyleneimino; alkoxy; oxo) must be regarded as a third one. A general pharmacophore model suitable for hypoglycemic benzoic acid derivatives, SUs, and sulfonamides is proposed (Figure 6). Furthermore, from superpositions of low-energy conformations (LECs) of 1, 2, and (S)-6al, it was concluded that a common binding conformation (LEC II; Figure 10B) may exist and that differences in binding to the SU receptor and in the mechanism of insulin release between repaglinide and the two SUs may be due to specific hydrophobic differences.