105746-47-2

Basic information

• Product Name: Nateglinide Methyl Ester
• Synonyms: Nateglinide Methyl Ester;Nateglinide Impurity;(R)-methyl 2-((1r,4R)-4-isopropylcyclohexanecarboxamido)-3-phenylpropanoate
• CAS NO: 105746-47-2
• Molecular Formula: C₂₀H₂₉NO₃
• Molecular Weight: 331.44916
• Mol File: 105746-47-2.mol

Chemical Properties

• Appearance: /
• CAS DataBase Reference: Nateglinide Methyl Ester(CAS DataBase Reference)
• NIST Chemistry Reference: Nateglinide Methyl Ester(105746-47-2)
• EPA Substance Registry System: Nateglinide Methyl Ester(105746-47-2)

Safety Data

• Hazardous Substances Data: 105746-47-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Research and Development:
Nateglinide Methyl Ester is used as a prodrug to improve the solubility and bioavailability of nateglinide for better absorption and effectiveness in the treatment of type 2 diabetes.
Used in Diabetes Management:
Nateglinide Methyl Ester is used as a pharmaceutical compound to increase the effectiveness of nateglinide in managing blood sugar levels in patients with type 2 diabetes.
Used in the Development of Improved Formulations:
Nateglinide Methyl Ester is utilized as a key component in the development of new and improved formulations of nateglinide, aiming to enhance the therapeutic outcomes for diabetes management across different patient populations.

Upstream product

• 21685-51-8 D-phenylalanine methyl ester 
• 67-56-1 methanol 
• 105816-04-4 nateglinide 
• 7077-05-6 trans-4-isopropylcyclohexane-1-carboxylic acid 
• 673-06-3 D-(R)-phenylalanine 
• 1245809-48-6 C₁₇H₂₄O₄S 
• 13033-84-6 D-phenylalanine methyl ester hydrochloride 
• 175284-00-1 p-menthan-7-oic acid methyl ester 

Downstream Products

• 594837-85-1 C₁₉H₂₆NO₃^(1-)*Na⁽¹⁺⁾ 
• 594837-86-2 C₁₉H₂₆NO₃^(1-)*K⁽¹⁺⁾ 
• 105816-04-4 nateglinide 

Relevant articles and documents

Green Esterification of Carboxylic Acids Promoted by tert-Butyl Nitrite

In this work, the green esterification of carboxylic acids promoted by tert-butyl nitrite has been well developed. This transformation is compatible with a broad range of substrates and exhibits excellent functional group tolerance. Various drugs and substituted amino acids are applicable to this reaction under near neutral conditions, with good to excellent yields.

Palladium-Catalyzed Late-Stage Direct Arene Cyanation

Methods for direct benzonitrile synthesis are sparse, despite the versatility of cyano groups in organic synthesis and the importance of benzonitriles for the dye, agrochemical, and pharmaceutical industries. We report the first general late-stage aryl C–H cyanation with broad substrate scope and functional-group tolerance. The reaction is enabled by a dual-ligand combination of quinoxaline and an amino acid-derived ligand. The method is applicable to direct cyanation of several marketed small-molecule drugs, common pharmacophores, and organic dyes. Benzonitriles are some of the most versatile building blocks for organic synthesis, in particular in the pharmaceutical industry, but general methods to make them by direct C–H functionalization are unknown. In this issue of Chem, Ritter and coworkers describe a late-stage aryl C–H cyanation with broad substrate scope and functional-group tolerance, enabled by a palladium-dual-ligand catalyst system. The reaction may serve for the late-stage modification of drug candidates. Aryl nitriles constitute an important class of organic compounds that are widely found in natural products, pharmaceuticals, agricultural chemicals, dyes, and materials. Moreover, nitriles are versatile building blocks to access numerous other important molecular structure groups. However, no general method for direct aromatic C–H cyanation is known. All approaches to date require either an appropriate directing group or reactive electron-rich substrates, such as indoles, which limit their synthetic applications. Here we describe an undirected, palladium-catalyzed late-stage aryl C–H cyanation reaction for the synthesis of complex aryl nitriles that would otherwise be more challenging to produce. The wide substrate scope and good functional-group tolerance of this reaction provide direct and quick access to structural diversity for pharmaceutical and agrochemical development.

A PROCESS FOR THE PREPARATION OF NATEGLINIDE

The present invention relates to a process for the preparation of substantially pure nateglinide of formula (I), substantially free from the cis-isomer and L-enantiomer and preparation of enantiomerically pure nateglinide form B, directly from the hydrolysis of a (-)-N-(trans-4-isopropylcyclohexyl-1-carbonyl)-D-phenylalanine alkyl ester in a ketonic solvent or water or mixture thereof.

A PROCESS FOR THE PREPARATION OF N-[[TRANS-4-(1-METHYLETHYL)CYCLOHEXYL]CARBONYL]-D-PHENYLALANINE

The present invention is directed to an novel, industrially viable and cost effective process for preparation of substantially pure N-[[trans-4-(l-methylethyl) cyclohexyl] carbonyl]-D- phenylalanine commonly known as Nateglinide.

PROCESS FOR THE PREPARATION OF NATEGLINIDE

One-pot process for the preparation of nateglinide, which process comprises reacting an alkyl ester of D-phenylalanine of formula (II) where R represents C1-4alkyl, typically methyl, either as the free base or in salt form (typically the hydrochloride), with trans-4-isopropylcyclohexanecarboxylic acid of formula (III) where X represents hydroxy or halo, typically chloro, to obtain a C1-4 alkyl ester of nateglinide of formula (IV), preferably the methyl ester of nateglinide followed by hydrolysis to yield nateglinide of formula (I).

Process for the preparation of nateglinide, preferably in b-form

The present invention relates to a process for the preparation of nateglinide, preferably in B-form, substantially free from the H-form, comprising three steps starting from D-phenylalanine methyl ester or a salt thereof.

N-(Cyclohexylcarbonyl)-D-phenylalanines and related compounds. A new class of oral hypoglycemic agents. 2

A series of analogues of N-(cyclohexylcarbonyl)-D-phenylalanine (5) have been synthesized and evaluated for their hypoglycemic activity. Relationships were studied between the activity and the three-dimensional structure of the acyl moiety, which was characterized by high-resolution 1H NMR spectroscopy and MNDO calculations. The role of the carboxyl group of the phenylalanine moiety was also studied by comparing the activities of the enantiomers, the decarboxyl derivative, the esters, and the amides of the phenylalanine derivatives. Thus, the structural requirements for possessing hypoglycemic activity was elucidated and a highly active compound, N-[(trans-4-isopropylcyclohexyl)carbonyl]-D-phenylalanine (13) was obtained, which showed a 20% blood glucose decrease at an oral dose of 1.6 mg/kg in fasted normal mice.