5448-16-8

Usage

Uses

Used in Pharmaceutical Research:
3-METHYL-1H-PYRROLE 2,4-DICARBOXYLIC ACID DIETHYL ESTER is used as a building block for the synthesis of novel organic compounds and pharmaceuticals due to its unique structure and properties.
Used in Drug Development:
In the pharmaceutical industry, 3-METHYL-1H-PYRROLE 2,4-DICARBOXYLIC ACID DIETHYL ESTER is used as a precursor in the development of new drugs, leveraging its potential applications in creating innovative therapeutic agents.

InChI:InChI=1/C11H15NO4/c1-4-15-10(13)8-6-12-9(7(8)3)11(14)16-5-2/h6,12H,4-5H2,1-3H3

Upstream product

• 4458-69-9 diethyl 5-bromo-3-methylpyrrole-2,4-dicarboxylate 
• 37789-75-6 3,5-diethoxycarbonyl-4-methylpyrrole-2-carboxylic acid 
• 84033-51-2 (E)-2-((Z)-2-Ethoxycarbonyl-vinylamino)-but-2-enoic acid ethyl ester 
• 75-05-8 acetonitrile 
• 328247-65-0 2-((E)-2-Ethoxycarbonyl-vinyl)-4-methyl-5-oxo-2,5-dihydro-isoxazole-3-carboxylic acid ethyl ester 
• 2999-46-4 Ethyl isocyanoacetate 
• 75-07-0 acetaldehyde 
• 134653-70-6 ethyl 2-[(dimethylamino)methylene]-3-oxobutanoate 
• 141-97-9 ethyl acetoacetate 
• 222718-74-3 C₁₄H₂₂N₂O₅ 
• 2199-60-2 diethyl 5-formyl-3-methylpyrrole-2,4-dicarboxylate 
• 4341-76-8 Ethyl 2-butynoate 
• 224315-82-6 (Z,E)-ethyl 2-(2-acetyl-2-ethoxycarbonyl-1-ethenyl)amino-3-dimethylaminopropenoate 
• 2436-79-5 diethyl 2,4-dimethylpyrrole-3,5-dicarboxylate 

Downstream Products

• 3780-41-4 3-methyl-1H-pyrrole-2,4-dicarboxylic acid 
• 90610-58-5 4-ethoxycarbonyl-3-methylpyrrole-2-carboxylic acid 
• 90610-57-4 3-methyl-pyrrole-2,4-dicarboxylic acid-2-ethyl ester 
• 5462-34-0 5-iodo-3-methyl-pyrrole-2,4-dicarboxylic acid diethyl ester 
• 94743-11-0 diethyl 3,5<13C>-dimethylpyrrole-2,4-dicarboxylate 
• 100129-92-8 diethyl 5-chloro-3-methylpyrrole-2,4-dicarboxylate 
• 427878-69-1 1-amino-3-methyl-1H-pyrrole-2,4-dicarboxylic acid diethyl ester 
• 427878-70-4 ethyl 4-hydroxy-5-methylpyrrolo[2,1-f ][1,2,4]-triazine-6-carboxylate 
• 779323-03-4 6-Amino-5-methyl-4-[(4-phenoxyphenyl)amino]pyrrolo[1,2-b]pyridazine-3-carbonitrile 
• 612083-63-3 6-Hydroxy-5-methyl-4-(4-phenoxy-phenylamino)-pyrrolo[1,2-b]pyridazine-3-carbonitrile 
• 612082-29-8 3-Cyano-5-methyl-4-[(4-phenoxyphenyl)amino]pyrrolo[1,2-b]pyridazine-6-carboxylic acid 
• 612083-62-2 6-(1-Hydroxy-1-methyl-ethyl)-5-methyl-4-(4-phenoxy-phenylamino)-pyrrolo[1,2-b]pyridazine-3-carbonitrile 
• 612082-33-4 3-(Aminomethyl)-5-methyl-4-[(4-phenoxyphenyl)amino]pyrrolo[1,2-b]pyridazine-6-carboxylic acid 
• 612083-24-6 3-Cyano-5-methyl-4-[(4-phenoxyphenyl)amino]pyrrolo[1,2-b]pyridazine-6-carboxylic acid ethyl ester 

Relevant academic research and scientific papers

TYROSINE KINASE INHIBITOR AND PHARMACEUTICAL COMPOSITION COMPRISING SAME

The present invention relates to a tyrosine kinase inhibitor and a pharmaceutical composition comprising same. The tyrosine kinase inhibitor of the present invention has the structures as shown in the following formula (I) or (II):

Exploration of novel pyrrolo[2,1-f][1,2,4]triazine derivatives with improved anticancer efficacy as dual inhibitors of c-Met/VEGFR-2

c-Met and VEGFR-2 have attracted interest as novel targets for treatment of various cancers. Aiming to develop potent dual c-Met and VEGFR-2 inhibitors, a series of pyrrolo[1,2-f][1,2,4]triazine derivatives were designed and synthesized. The majority of target compounds exhibited potent antiproliferative effect against c-Met addictive cancer cell lines with IC50 values ranged from 1.2 to 24.6 nM, especially 27a. In-depth studies demonstrated 27a has great selectivity to c-Met and VEGFR-2, and potent inhibitory activity against them (IC50 of 2.3 ± 0.1 nM and 5.0 ± 0.5 nM). Furthermore, it also showed the highest anticancer activity with IC50 of 0.71 ± 0.16 nM (better than the positive compound) against BaF3-TPR-Met and 37.4 ± 0.311 nM (comparable to the positive compound) against HUVEC-VEGFR2, consistent with that in c-Met sensitive tumor cell lines. Subsequently, physicochemical and pharmacokinetic characterization indicated 27a has favorable druggability and pharmacokinetic properties. Further docking studies suggested a common mode of interaction at the ATP-binding site of c-Met and VEGFR-2, also indicating that 27a was a potential candidate for cancer therapy deserving further study.

Development of a practical synthesis of a p38 kinase inhibitor via a safe and robust amination

The development of a practical synthesis for a p38 kinase inhibitor is described. The key advances include an improved route to the key intermediate, a substituted pyrrole, and a subsequent animation utilizing O-(4-nitrobenzoyl)- hydroxylamine, which provides a safe, scalable, and robust amination method. The new protocol was successfully demonstrated to generate 1.6 kg of API in seven steps and 26% overall yield.

Development of a practical synthesis of a functionalized pyrrolo[2,1-f][1,2,4]triazine nucleus

Functionalized pyrrolotriazine 1b is a key heterocyclic building block in the synthesis of BMS-690514, a potent anticancer agent. Described herein are our development activities that led to the efficient preparation of 1b on a large scale. The key transformations include a selective C-alkylation of an oxalacetate salt with a hydrazonyl bromide to form a 2-hydrazonoethyl-3- oxosuccinate, followed by cyclodehydration to an aminopyrrole. Subsequent deprotection and condensation with formamidine afforded the pyrrolotriazine scaffold. Further elaboration of this core provided the desired pyrrolotriazinyl amine.

Pyrrolopyridazine MEK inhibitors

The synthesis and SAR of a series of pyrrolopyridazine MEK inhibitors are reported. Optimal activity was achieved by incorporation of a 4-phenoxyaniline substituent at C4 and an acylated amine at C6.

Remarkable solvent effect in Barton-Zard pyrrole synthesis: application in an efficient one-step synthesis of pyrrole derivatives

A unique solvent effect encountered in the Barton-Zard pyrrole synthesis was exploited to develop an efficient synthesis of pyrrole-2-esters. The chemistry was extended to a one-pot synthesis of pyrrole-2,4-dicarboxylates.

Process for preparing salts of 4-[[5-[(cyclopropylamino)carbonyl]-2-methylphenyl]amino]-5-methyl-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide and novel stable forms produced therein

Processes are provided for selectively preparing novel stable crystalline salt forms, selectively and consistently, namely, preparing Form N-1 of the methanesulfonic acid salt, and Form N-1 and Form N-4 of the hydrochloric acid salt of the p38 kinase inhibitor 4-[[5-[(cyclopropylamino)carbonyl]-2-methylphenyl]amino]-5-methyl-N-propylpyrrolo[2,1-f][1,2,4]triazine-6-carboxamide. The processes preferably employ solvent systems including formic acid/acetone and formic acid/methylethyl ketone which produce crystals having suitable flow properties and desired particle size, and solvents such as N,N-dimethylformamide and N,N-dimethylacetamide may be employed as well. Novel Form N-1 crystals of the Form N-1 and Form N-4 crystals of the hydrochloride salt and Form N-1 crystals of the methanesulfonic acid salt of the above free base, pharmaceutical compositions containing such novel forms and a method of treating p38 kinase associated conditions, including rheumatoid arthritis are also provided.

Methods for the preparation of pyrrolotriazine compounds

A method for preparing a compound having the formula: including the steps of: (a) cyclizing a compound of formula II: to form a compound of formula I: (b) deprotecting the nitrogen atom of the compound of formula I by amination or hydrogenation to form compound III.

New dual inhibitors of EGFR and HER2 protein tyrosine kinases

A novel series of dual EGFR and HER2 inhibitors based on the pyrrolo[2,1-f][1,2,4]triazine nucleus is described. A general route toward their synthesis, which enables functionalization at multiple sites, has been developed. Biological evaluation in enzyma

Copper- or phosphine-catalyzed reaction of alkynes with isocyanides. Regioselective synthesis of substituted pyrroles controlled by the catalyst

The copper-catalyzed reaction of isocyanides (CNCH2EWG 1) 1 with electron-deficient alkynes (RC=CEWG2) 2 gave the 2,4-di-EWG-substituted pyrroles 3 selectively, whereas the phosphine-catalyzed reaction of 1 with 2 afforded