62535-60-8

Usage

Uses

Used in Pharmaceutical Industry:
5-Amino-3-methyl-1-p-tolylpyrazole is used as a key intermediate in the synthesis of various biologically active compounds for pharmaceutical applications. Its unique chemical structure and properties contribute to the development of new drugs aimed at treating a wide range of diseases and medical conditions.
Used in Agrochemical Industry:
In the agrochemical sector, 5-Amino-3-methyl-1-p-tolylpyrazole is utilized as a building block for the creation of novel agrochemicals. Its potential role in the synthesis of compounds with pesticidal or herbicidal properties makes it a valuable resource for addressing pest and weed control challenges in agriculture.
Overall, the diverse applications of 5-Amino-3-methyl-1-p-tolylpyrazole across the pharmaceutical and agrochemical industries highlight its significance as a versatile and promising intermediate in the development of innovative solutions for health and agriculture.

InChI:InChI=1/C11H13N3/c1-8-3-5-10(6-4-8)14-11(12)7-9(2)13-14/h3-7H,12H2,1-2H3

Upstream product

• 91331-63-4 3-p-tolylhydrazono-butyronitrile 
• 637-60-5 p-tolylhydrazine hydrochloride 
• 1118-60-1 3-iminobutyronitrile 
• 539-44-6 N-4-methylphenylhydrazine 
• 1118-61-2 3-Aminocrotononitrile 
• 2469-99-0 Cyanoaceton 

Downstream Products

• 90094-70-5 1-(4-Methylphenyl)-3-methyl-4-nitroso-5-amino-pyrazole 
• 956574-51-9 2-[(5-methyl-2-p-tolyl-2H-pyrazol-3-ylamino)-methylene]-malonic acid diethyl ester 
• 90094-69-2 3-Methyl-1-p-tolyl-1H-pyrazolo[3,4-b]pyrazine-5,6-dicarboxylic acid diethyl ester 
• 1038741-35-3 C₁₁H₁₂IN₃ 
• 882226-74-6 1-[5-amino-3-methyl-1-(4-methylphenyl)-1H-pyrazol-4-yl]-2,2,2-trifluoro-1-(1-methyl-1H-imidazol-2-yl)ethanol 
• 866040-20-2 4-chloro-3-methyl-1-p-tolyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ethyl ester 
• 1610411-15-8 3-methyl-4-(3-methyl-5-phenyl-1-(p-tolyl)-1,6-dihydropyrrolo-[2,3-c]pyrazol-4-yl)-1-(p-tolyl)-1H-pyrazol-5-amine 
• 1602492-66-9 (E)-1,2-bis(4-iodo-3-methyl-1-p-tolyl-1H-pyrazol-5-yl)diazene 

Relevant academic research and scientific papers

Improvement of Oral Bioavailability of Pyrazolo-Pyridone Inhibitors of the Interaction of DCN1/2 and UBE2M

The cullin-RING ubiquitin ligases (CRLs) are ubiquitin E3 enzymes that play a key role in controlling proteasomal degradation and are activated by neddylation. We previously reported inhibitors that target CRL activation by disrupting the interaction of defective in cullin neddylation 1 (DCN1), a CRL neddylation co-E3, and UBE2M, a neddylation E2. Our first-generation inhibitors possessed poor oral bioavailability and fairly rapid clearance that hindered the study of acute inhibition of DCN-controlled CRL activity in vivo. Herein, we report studies to improve the pharmacokinetic performance of the pyrazolo-pyridone inhibitors. The current best inhibitor, 40, inhibits the interaction of DCN1 and UBE2M, blocks NEDD8 transfer in biochemical assays, thermally stabilizes cellular DCN1, and inhibits anchorage-independent growth in a DCN1 amplified squamous cell carcinoma cell line. Additionally, we demonstrate that a single oral 50 mg/kg dose sustains plasma exposures above the biochemical IC90 for 24 h in mice.

Chiral Phosphoric Acid-Catalyzed Enantioselective Synthesis of Pyrazole-Based Unnatural α-Amino Acid Derivatives

An enantioselective synthesis of unnatural pyrazole-based α-chiral amino acid derivatives from the asymmetric reaction of N-aryl-5-aminopyrazoles with β,γ-alkynyl-α-imino esters using a chiral spirocyclic phosphoric acid catalyst was developed. Using the established methodology, various pyrazole-based α-amino acid derivatives with tetrasubstituted carbon stereocenters were obtained in 67–98% yields and with 73–99% enantioselectivities. The NH2 functionality in the corresponding products enables further transformations to a chiral thiourea and a lactam. (Figure presented.).

Oxidative Ring-Opening of 1H-Pyrazol-5-amines and Its Application in Constructing Pyrazolo–Pyrrolo–Pyrazine Scaffolds by Domino Cyclization

Herein, an oxidative ring-opening of 1H-pyrazol-5-amines to form 3-diazenylacrylonitrile derivatives under mild and transition-metal-free conditions is described. In addition, the nucleophilic addition of deprotonated 1H-pyrrole-2-carbaldehydes to the vinyl moiety of the yielded 3-diazenylacrylonitriles could trigger domino cyclization to afford the 3H-pyrazolo[3,4-e]pyrrolo[1,2-a]pyrazine derivatives. Computational studies suggest that the oxidation of 1H-pyrazol-5-amines in the presence of PhIO is through the formation of a hydroxylamine intermediate followed by elimination of H2O to result in the ring-opening product. The detailed domino cyclization pathway leading to the pyrazolo–pyrrolo–pyrazine scaffolds is revealed.

Microwave synthesis of 1-aryl-1H-pyrazole-5-amines

A microwave-mediated synthesis of 1H-pyrazole-5-amines utilizing 1 M HCl at 150 °C was developed in order to provide products in a matter of minutes with minimal purification. Most reactions are complete in only 10 min and can be isolated via a simple filtration without the need for further purification by column chromatography or recrystallization. This method tolerates a range of functional groups and can be performed on milligram to gram scales.

Multicomponent Dipolar Cycloaddition Strategy: Combinatorial Synthesis of Novel Spiro-Tethered Pyrazolo[3,4-b]quinoline Hybrid Heterocycles

The stereoselective syntheses of a library of novel spiro-tethered pyrazolo[3,4-b]quinoline-pyrrolidine/pyrrolothiazole/indolizine-oxindole/acenaphthene hybrid heterocycles have been achieved through the 1,3-dipolar cycloaddition of azomethine ylides generated in situ from α-amino acids and 1,2-diketones to dipolarophiles derived from pyrazolo[3,4-b]quinoline derivatives.

Pyrazole[3,4-e][1,4]thiazepin-7-one derivatives as a novel class of Farnesoid X Receptor (FXR) agonists

A virtual screening procedure was applied to the discovery of structurally diverse non-steroidal Farnesoid X Receptor (FXR) agonists. From 117 compounds selected by virtual screening, a total of 47 compounds were found to be FXR agonists, with 34 of them showing activity below a concentration of 20 μM. 1H-Pyrazole[3,4-e][1,4]thiazepin-7-one-based hit compound 7 was chosen for hit-to-lead optimization. A large number of 1H-pyrazole[3,4-e][1,4]thiazepin-7- one derivatives was designed, synthesized, and evaluated by a cell-based luciferase transactivation assay for their agonistic activity against FXR. Most of them exhibited low micromolar range of potency and very high efficacy.

Approach to the library of fused pyridine-4-carboxylic acids by combes-type reaction of acyl pyruvates and electron-rich amino heterocycles

A library of fused pyridine-4-carboxylic acids (including pyrazolo[3,4-b]pyridines, isoxazolo[5,4-b]pyridines, furo[2,3-b]pyridines, thieno[2,3-b]pyridines, and pyrido[2,3-d]pyrimidines) was generated by Combes-type reaction of acyl pyruvates and electron-rich amino heterocycles followed by hydrolysis of the ester. The library members were also demonstrated to undergo the standard combinatorial transformations including amide coupling and esterification, as well as less common heterocyclizations to 1,2,4-triazoles and 1,2,4-oxadiazoles.

The identification a novel, selective, non-steroidal, functional glucocorticoid receptor antagonist

The identification of novel, potent, non-steroidal/small molecule functional GR antagonist GSK1564023A selective over PR is described. Associated structure-activity relationships and the process of optimisation of an initial HTS hit are also described.

Synthesis of N(1)-substituted 5-amino-3-methylpyrazoles

With the aim of preparing new biologically active compounds a series of N(1)-substituted 5-amino-3-methylpyrazoles has been obtained from β-aminocrotononitrile and mono-substituted hydrazines.