33369-52-7

Basic information

• Product Name: methyl 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetate
• Synonyms: methyl 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetate;METHYL 1-METHYL-5-(P-TOLUOYL)-2-PYRROLYLACETAT;1-Methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetic acid methyl ester;TolMetin Methyl ester;SIXINSDWVSIFEY-UHFFFAOYSA-N
• CAS NO: 33369-52-7
• Molecular Formula: C₁₆H₁₇NO₃
• Molecular Weight: 271.31108
• EINECS: 251-480-5
• Mol File: 33369-52-7.mol

Chemical Properties

• Boiling Point: 427.6 °C at 760 mmHg
• Flash Point: 212.4 °C
• Appearance: /
• Density: 1.11
• Vapor Pressure: 1.62E-07mmHg at 25°C
• Refractive Index: 1.553
• PKA: -8.00±0.70(Predicted)
• CAS DataBase Reference: methyl 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetate(CAS DataBase Reference)
• NIST Chemistry Reference: methyl 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetate(33369-52-7)
• EPA Substance Registry System: methyl 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetate(33369-52-7)

Safety Data

• Hazardous Substances Data: 33369-52-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Research:
Methyl 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetate is utilized as a key intermediate in the synthesis of pharmaceuticals. Its distinctive structure allows it to be incorporated into the design and production of novel drug molecules, potentially leading to the discovery of new treatments for various diseases and conditions.
Used in Agrochemical Development:
In the agrochemical industry, this compound is employed as a precursor in the synthesis of various agrochemicals. Its use in this field contributes to the development of innovative products aimed at enhancing crop protection and improving agricultural yields.
Used in Material Science:
Methyl 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetate also finds potential applications in material science due to its intriguing chemical properties. Researchers and industry professionals explore its potential in creating new materials with unique characteristics for various applications.
It is crucial to handle methyl 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetate with care, as it may pose health and environmental risks if not managed properly. Proper safety measures and disposal methods should be adhered to when working with this compound.

InChI:InChI=1/C16H17NO3/c1-11-4-6-12(7-5-11)16(19)14-9-8-13(17(14)2)10-15(18)20-3/h4-9H,10H2,1-3H3

Upstream product

• 55174-52-2 4,N-dimethyl-benzimidoyl chloride 
• 51856-79-2 N-methyl-2-(methoxycarbonylmethyl)pyrrole 
• 144-55-8 sodium hydrogencarbonate 
• 563-43-9 ethylaluminum dichloride 
• 874-60-2 4-methyl-benzoyl chloride 
• 63833-44-3 morpholino(p-tolyl)methanone 
• 96-54-8 N-Methylpyrrole 
• 21898-59-9 1-methylpyrrole-2-acetic acid 
• 21898-43-1 2-(1-methyl-1H-pyrrol-2-yl)-2-oxoacetic acid 
• 26171-23-3 1-methyl-5-(p-toluoyl)pyrrole-2-acetic acid 
• 85622-93-1 temozolomide 
• 83846-84-8 C₉H₁₁NO₄ 
• 83863-74-5 2-(carboxymethyl)-1-methyl-1H-pyrrole-3-carboxylic acid 
• 617721-38-7 methyl 2-(5-(4-cyanobenzoyl)-1-methyl-1H-pyrrol-2-yl)acetate 

Downstream Products

• 62380-67-0 methyl 3-chloro-1-methyl-5-(p-toluoyl)pyrrole-2-acetate 
• 35711-34-3 tolmetin sodium 
• 26171-23-3 1-methyl-5-(p-toluoyl)pyrrole-2-acetic acid 

Relevant articles and documents

Synthetic method of non-steroidal antiinflammatory drug pain killing

The invention discloses a synthesis method of non-steroidal anti-inflammatory drug tolmetin. The methodcomprises the following steps: sequentially preparing a sulfuric acid-containing acetonedicarboxylic acid crude product, 2-(2-acetoxy)-1-methyl-1H-pyrrole-3-formic acid and 2-(2-alkyl acetate)-1-methyl-1H-pyrrole-3-formic acid by taking citric acid or citric acid monohydrate as a raw material; and carrying out decarboxylation, acylation, hydrolysis and acidification to obtain tolmetin. The synthetic method provided by the invention overcomes the defect that the existing tolmetin preparation process depends on N-methylpyrrole, and is a low-cost, low-pollution and high-yield synthetic method of non-steroidal anti-inflammatory drug tolmetin.

Design, synthesis, anticancer evaluation, and molecular modelling studies of novel tolmetin derivatives as potential VEGFR-2 inhibitors and apoptosis inducers

Novel tolmetin derivatives 5a–f to 8a–c were designed, synthesised, and evaluated for antiproliferative activity by NCI (USA) against a panel of 60 tumour cell lines. The cytotoxic activity of the most active tolmetin derivatives 5b and 5c was examined against HL-60, HCT-15, and UO-31 tumour cell lines. Compound 5b was found to be the most potent derivative against HL-60, HCT-15, and UO-31 cell lines with IC50 values of 10.32 ± 0.55, 6.62 ± 0.35, and 7.69 ± 0.41 μM, respectively. Molecular modelling studies of derivative 5b towards the VEGFR-2 active site were performed. Compound 5b displayed high inhibitory activity against VEGFR-2 (IC50 = 0.20 μM). It extremely reduced the HUVECs migration potential exhibiting deeply reduced wound healing patterns after 72 h. It induced apoptosis in HCT-15 cells (52.72-fold). This evidence was supported by an increase in the level of apoptotic caspases-3, -8, and -9 by 7.808-, 1.867-, and 7.622-fold, respectively. Compound 5b arrested the cell cycle in the G0/G1 phase. Furthermore, the ADME studies showed that compound 5b possessed promising pharmacokinetic properties.

Imidazotetrazines as Weighable Diazomethane Surrogates for Esterifications and Cyclopropanations

Diazomethane is one of the most versatile reagents in organic synthesis, but its utility is limited by its hazardous nature. Although alternative methods exist to perform the unique chemistry of diazomethane, these suffer from diminished reactivity and/or correspondingly harsher conditions. Herein, we describe the repurposing of imidazotetrazines (such as temozolomide, TMZ, the standard of care for glioblastoma) for use as synthetic precursors of alkyl diazonium reagents. TMZ was employed to conduct esterifications and metal-catalyzed cyclopropanations, and results show that methyl ester formation from a wide variety of substrates is especially efficient and operationally simple. TMZ is a commercially available solid that is non-explosive and non-toxic, and should find broad utility as a replacement for diazomethane.

Isotope labelling by reduction of nitriles: Application to the synthesis of isotopologues of tolmetin and celecoxib

The aryl methyl group is found in many drug-like compounds, but there are limited ways of preparing compounds with an isotope label in this methyl position. The process of cyanation of an aryl halide followed by complete reduction of the nitrile to a methyl group was investigated as a route for preparing stable and radiolabelled isotopologues of drug-like compounds. Using this methodology, carbon-13, deuterium, carbon-14, and tritium labelled isotopologues of the nonsteroidal anti-inflammatory drug tolmetin were produced, as well as carbon-13, deuterium, and carbon-14 labelled isotopologues of another nonsteroidal anti-inflammatory drug, celecoxib. The radiolabelled compounds were produced at high specific activity and the stable isotope labelled compounds with high incorporation making them suitable for use as internal standards in mass spectrometry assays. This approach provides a common synthetic route to multiple isotopologues of compounds using inexpensive and readily available labelled starting materials.

Synthesis of Tolmetin Hydrazide-Hydrazones and Discovery of a Potent Apoptosis Inducer in Colon Cancer Cells

Tolmetin hydrazide and a novel series of tolmetin hydrazide-hydrazones 4a-l were synthesized in this study. The structures of the new compounds were determined by spectral (FT-IR, 1H NMR) methods. N′-[(2,6-Dichlorophenyl)methylidene]-2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetohydrazide (4g) was evaluated in vitro using the MTT colorimetric method against the colon cancer cell lines HCT-116 (ATCC, CCL-247) and HT-29 (ATCC, HTB-38) to determine growth inhibition and cell viability at different doses. Compound 4g exhibited anti-cancer activity with an IC50 value of 76 μM against colon cancer line HT-29 (ATCC, HTB-38) and did not display cytotoxicity toward control NIH3T3 mouse embryonic fibroblast cells compared to tolmetin. In addition, this compound was evaluated for caspase-3, caspase-8, caspase-9, and annexin-V activation in the apoptotic pathway, which plays a key role in the treatment of cancer. We demonstrated that the anti-cancer activity of this compound was due to the activation of caspase-8 and caspase-9 involved in the apoptotic pathway. In addition, in this study, we investigated the catalytical effect of COX on the HT-29 cancer line, the apoptotic mechanism, and the moleculer binding of tolmetin and compound 4g on the COX enzyme active site. The tolmetin hydrazone N′-[(2,6-dichlorophenyl)methylidene]-2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetohydrazide (4g) exhibited anticancer activity with an IC50 value of 76 μM against HT-29 cells and did not display cytotoxicity toward control fibroblast cells, compared to tolmetin. The anti-cancer activity of 4g was shown to be due to the activation of caspase-8 and caspase-9 involved in apoptosis.

An Electrophilic Approach to the Palladium-Catalyzed Carbonylative C-H Functionalization of Heterocycles

A palladium-catalyzed approach to intermolecular carbonylative C-H functionalization is described. This transformation is mediated by PtBu3-coordinated palladium catalyst and allows the derivatization of a diverse range of heterocycles, including pyrroles, indoles, imidazoles, benzoxazoles, and furans. Preliminary studies suggest that this reaction may proceed via the catalytic formation of highly electrophilic intermediates. Overall, this provides with an atom-economical and general synthetic route to generate aryl-(hetero)aryl ketones using stable reagents (aryl iodides and CO) and without the typical need to exploit pre-metalated heterocycles in carbonylative coupling chemistry.

Friedel - Crafts acylation of pyrroles and indoles using 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) as a nucleophilic catalyst

1,5-Diazabicyclo[4.3.0]non-5-ene (DBN) has been shown to be an effective catalyst for the regioselective Friedel - Crafts C-acylation of pyrroles and indoles in high yields. A detailed mechanistic study implies that DBN is acting as a nucleophilic organocatalyst, with the X-ray crystal structure of a key N-acyl-amidine intermediate having been determined for the first time.

Synthesis and process optimization of amtolmetin: An antiinflammatory agent

Efforts toward the synthesis and process optimization of amtolmetin guacil 1 are described. High-yielding electrophilic substitution followed by Wolf-Kishner reduction are the key features in the novel synthesis of tolmetin 2 which is an advanced intermediate of 1.

PROCESS FOR PRODUCING 2-[1-METHYL-5-(4-METHYLBENZOYL)- PYRROL-2- YL]ACETIC ACID OR SALT THEREOF

The present invention relates to novel process for the preparation of tolmetin sodium, by employing easily available starting material and suitable reaction conditions. This invention is further related to novel crystalline forms of tolmetin methyl ester, tolmetin and tolmetin sodium and their process for the preparation.

Imidoyl substituted pyrroles

Novel compounds, which are aryl-pyrrolyl-imine derivatives of the Formula I STR1 and acid addition salts thereof are disclosed; which compounds may be prepared by the acid catalyzed condensation of an imidoyl chloride with a lower alkyl pyrrole-2-acetate; and which compounds are useful as intermediates to form by hydrolysis, the known useful ketone analogs which have anti-inflammatory and analgesic activity; and certain of which compounds have antisecretory, anti-irritable bowel, antidiarrheal and general behavior effect on the CNS properties.