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Usage

Uses

Used in Pharmaceutical Industry:
Ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate is used as a synthetic intermediate for the development of various pharmaceutical compounds. Its unique structure allows for the creation of new molecules with potential therapeutic applications, contributing to the advancement of drug discovery and development.
Used in Agrochemical Industry:
Ethyl 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylate is used as a key intermediate in the synthesis of 3-difluoromethylpyrazole-carboxamide fungicides. These fungicides are designed to protect crops from fungal infections, ensuring higher yields and better quality produce. The compound's role in the development of these fungicides highlights its importance in the agrochemical industry.

InChI:InChI=1/C8H10F2N2O2/c1-3-14-8(13)5-4-12(2)11-6(5)7(9)10/h4,7H,3H2,1-2H3

Upstream product

• 851725-87-6 ethyl 3-(dichloromethyl)-1-methyl-1H-pyrazole-4-carboxylate 
• 1086400-66-9 (Z)-2-(ethoxymethylene)-4,4-difluoro-3-oxobutanoic acid ethyl ester 
• 60-34-4 methylhydrazine 
• 176969-33-8 (E/Z)-ethyl 2-(ethoxymethylene)-4,4-difluoro-3-oxobutanoate 
• 64-17-5 ethanol 
• 1089212-38-3 4-bromo-3-(difluoromethyl)-1-methyl-1H-pyrazole 
• 201230-82-2 carbon monoxide 
• 72153-33-4 1-methyl-2-dfluoroacetylhydrazine 
• 623-47-2 propynoic acid ethyl ester 
• 1094495-17-6 4,4-difluoro-2-[1-methylamino-meth-(E)-ylidene]-3-oxo-butyric acid ethyl ester 
• 571-55-1 ethyl 2-(ethoxymethylidene)-4,4,4-trifluoro-3-oxobutanoate 
• 924-99-2 ethyl 3-(dimethylamino)acrylate 
• 2925-22-6 2,2-difluoroacetyl fluoride 
• 1186318-47-7 ethyl 4,4-difluoro-2-[1-{N-methyl-N'-[1-phenylmethylidene]hydrazino}-methylidene]-3-oxobutyrate 

Downstream Products

• 956481-28-0 3-(difluoromethyl)-1-methyl-N-(2-biphenyl)-4-pyrazole carboxamide 
• 1373886-87-3 C₁₃H₁₂F₃N₃O 
• 1373886-86-2 C₁₂H₁₀F₃N₃O 
• 1373886-88-4 C₁₂H₈Cl₃F₂N₃O 
• 581809-46-3 bixafen 
• 874967-67-6 sedaxane 
• 881685-58-1 isopyrazam 

Relevant academic research and scientific papers

Crystal structure and molecular docking studies of new pyrazole-4-carboxamides

Two pyrazol-4-carboxamides, 3-(difluoromethyl)-N-(mesitylcarbamoyl)-1-methyl-1H-pyrazole-4-carboxa-mide (7a) and 3-(difluoromethyl)-N-((3,5-dimethylphenyl) carbamoyl)-1-methyl-1H-pyrazole-4-carboxamide (7b) were synthesized and their structures were confirmed by the aid of 1H NMR and HRMS analyses. The structure of the pyrazole-4-carboxamide, 7a was also determined by X-ray diffraction. The preliminary activity results demonstrate that these two compounds exhibit good inhibitory activity against Botrytis cinerea. Further docking results indicated that the key active group is difluoromethyl pyrazole moiety.

An atom-efficient route to ethyl 3-(difluoromethyl)-1-methyl-1 H-pyrazole-4-carboxylate (DFMMP)-A key building block for a novel fungicide family

A growing number of fluorine-containing active ingredients in the pharmaceutical and agrochemical industries inevitably raises the demand for new fluorinated building blocks. Their availability is mainly constricted by suitable chemistry and available bulk fluorine containing starting materials. Because of the high cost impact especially in the agrochemical industry, the choice of a synthetic route is heavily driven by economic aspects; thus, the environmental profile often is handled as a "secondary factor" or finally falls aside. DFMMP is a key building block for a fast growing new fungicide family, like Syngenta's Sedaxane, and BASF's Fluxapyroxad and Bayer's Bixafen currently made by environmetally less friendly routes. Herein we present a cost-competitive and green route, developed at Solvay laboratories, displaying significantly lower environmental impact.

Synthesis, nematocidal activity and SAR study of novel difluoromethylpyrazole carboxamide derivatives containing flexible alkyl chain moieties

A series of novel difluoromethylpyrazole carboxamides derivatives were synthesized by introduction of flexible alkyl chain. Nematicidal bioassay results showed that some of them exhibited good control efficacy against M. incognita, which indicated that these difluoromethylpyrazole carboxamides derivatives might be potential novel lead compounds for discovery new nematicides. The nematicidal activity was affected by the substituted position in the molecule, especially the substitution group on the alkyl chain. It was found that the compound 6-9 and 6-23 possess about 50% inhibition effect against M. incognita even at 5.0 and 1.0 mg L?1. Meanwhile, greenhouse field trial showed the nematicidal activity of compound 6-9 is a litter weaker than that of Abamectin. The mammalian toxicology results indicated that compound 6-9 was a low-toxicity and low-sensitive compound. In conclusion compound 6-9 is a potential candidate for further development. In addition, the molecular docking simulations revealed that compounds 6 with a flexible NHCOO show its binding affinities for the acetylcholine receptor (AChR), which may provide useful information for further design novel nematicides.

Synthesis and biological activity of acyl thiourea containing difluoromethyl pyrazole motif

A series of new acyl thiourea derivatives containing difluoromethyl pyrazole moiety were designed and synthesized. Their structures were confirmed by 1H NMR, 31C NMR, MS and HRMS. The bioassay results showed that some of title compounds exhibited good in vivo fungicidal activity against Botrytis cinerea and Fusarium oxysporum and good antibacterial activity against Pseudomonas syringae pv. Lachrymans at 50 mg/L respectively.

Synthesis, Crystal Structure, Antifungal Activity, and Docking Study of Difluoromethyl Pyrazole Derivatives

Nine novel difluoromethylpyrazole acyl urea derivatives were synthesized via seven steps conveniently. All the structures were determined by 1H-NMR, 13C-NMR, HRMS, and X-ray diffraction. The in vivo fungicidal activities were determined against Corynespora mazei, Botrytis cinerea, Fusarium oxysporum, and Pseudomonas syringae, respectively. The bioassay results indicated that some of them displayed good control effective (around 50 and 80%) against P. syringae and B. cinerea at 50 mg/L, respectively, which is better than control. It is possible that difluoromethylpyrazole acyl urea derivatives can be a leading compound for the development of new fungicides against the two fungi with further structure optimization. Furthermore, docking model was studied to establish structure–activity relationship of difluoromethylpyrazole acyl urea derivatives.

Expanding the Chemical Space of Succinate Dehydrogenase Inhibitors via the Carbon-Silicon Switch Strategy

The carbon-silicon switch strategy has become a key technique for structural optimization of drugs to widen the chemical space, increase drug activity against targeted proteins, and generate novel and patentable lead compounds. Flubeneteram, targeting succinate dehydrogenase (SDH), is a promising fungicide candidate recently developed in China. We describe the synthesis of novel SDH inhibitors with enhanced fungicidal activity to enlarge the chemical space of flubeneteram by employing the C-Si switch strategy. Several of the thus formed flubeneteram-silyl derivatives exhibited improved fungicidal activity against porcine SDH compared with the lead compound flubeneteram and the positive controls. Disease control experiments conducted in a greenhouse showed that trimethyl-silyl-substituted compound W2 showed comparable and even higher fungicidal activities compared to benzovindiflupyr and flubeneteram, respectively, even with a low concentration of 0.19 mg/L for soybean rust control. Furthermore, compound W2 encouragingly performed slightly better control than azoxystrobin and was less active than benzovindiflupyr at the concentration of 100 mg/L against soybean rust in field trials. The computational results showed that the silyl-substituted phenyl moiety in W2 could form strong van der Waals (VDW) interactions with SDH. Our results indicate that the C-Si switch strategy is an effective method for the development of novel SDH inhibitors.

Synthesis and preparation method of 4-pyrazole ethyl formate

The invention discloses a synthesis and preparation method of 4-pyrazole ethyl formate. The method comprises the following steps: dissolving ethyl 2-dichloroacetyl-3-(dimethylamino) acrylate in an organic solvent, and reacting with methylhydrazine to obtain ethyl 1-methyl-3-dichloromethyl-4-pyrazole formate; reacting the obtained ethyl 1-methyl-3-dichloromethyl-4-pyrazole formate with a fluorination reagent to obtain 1-methyl- 3-difluoromethyl-4-pyrazole ethyl formate; mixing 1-methyl- 3-difluoromethyl-4-pyrazole ethyl formate with glacial acetic acid, dropwise adding a strong acidic solutionat the temperature of 0 DEG C, and then adding dichloromethane and water for stirring and layering to obtain an organic layer; and recrystallizing the organic layer by using a mixed solvent of petroleum ether and ethyl acetate to obtain the 4-pyrazole ethyl formate. The method has the advantages of wide raw material source, low raw material price and simple preparation process, and the obtained product is easy to purify, low in production cost and suitable for large-scale industrial production.

PRODUCING METHOD FOR 3-DIFLUOROMETHYLPYRAZOLE COMPOUND, PRODUCING METHOD FOR 3-DIFLUOROMETHYLPYRAZOLE-4-CARBOXYLIC ACID COMPOUND, AND PYRAZOLIDINE COMPOUND

Provided are producing methods for a 3-difluoromethylpyrazole compound and a 3-difluoromethylpyrazole-4-carboxylic acid compound, which include, in a reaction solvent containing a specific solvent, subjecting a difluoroacetyl group-containing compound, a hydrazine compound, and formaldehyde to a cyclocondensation reaction, and subsequently oxidizing the obtained pyrazole compound precursor, and a pyrazolidine compound represented by a specific formula in these producing methods.

Expedient discovery for novel antifungal leads targeting succinate dehydrogenase: Pyrazole-4-formylhydrazide derivatives bearing a diphenyl ether fragment

The pyrazole-4-carboxamide scaffold containing a flexible amide chain has emerged as the molecular skeleton of highly efficient agricultural fungicides targeting succinate dehydrogenase (SDH). Based on the above vital structural features of succinate dehydrogenase inhibitors (SDHI), three types of novel pyrazole-4-formylhydrazine derivatives bearing a diphenyl ether moiety were rationally conceived under the guidance of a virtual docking comparison between bioactive molecules and SDH. Consistent with the virtual verification results of a molecular docking comparison, the in vitro antifungal bioassays indicated that the skeleton structure of title compounds should be optimized as an N′-(4-phenoxyphenyl)-1H-pyrazole-4-carbohydrazide scaffold. Strikingly, N′-(4-phenoxyphenyl)-1H-pyrazole-4-carbohydrazide derivatives 11o against Rhizoctonia solani, 11m against Fusarium graminearum, and 11g against Botrytis cinerea exhibited excellent antifungal effects, with corresponding EC50 values of 0.14, 0.27, and 0.52 μg/mL, which were obviously better than carbendazim against R. solani (0.34 μg/mL) and F. graminearum (0.57 μg/mL) as well as penthiopyrad against B. cinerea (0.83 μg/mL). The relative studies on an in vivo bioassay against R. solani, bioactive evaluation against SDH, and molecular docking were further explored to ascertain the practical value of compound 11o as a potential fungicide targeting SDH. The present work provided a non-negligible complement for the structural optimization of antifungal leads targeting SDH.

Preparation method and application of pyrazole derivative

The invention relates to a preparation method of a pyrazole derivative. The compound shown in the formula I reacts with a silanization reagent shown in a formula II to generate an intermediate productshown in a formula III, the intermediate product shown in the formula III reacts with a halogenated acid derivative shown in a formula IV to generate a halogenated compound shown in a formula V, andthe halogenated compound shown in the formula V reacts under acidic conditions to generate a pyrazole derivative shown in a formula VI. The preparation method of the pyrazole derivative is suitable for industrial production.