Day: February 9, 2023

A robust protocol for Pd(ii)-catalyzed C-3 arylation of (1H) indazoles and pyrazoles: total synthesis of nigellidine hydrobromide was written by Ye, Mengchun;Edmunds, Andrew J. F.;Morris, James A.;Sale, David;Zhang, Yejia;Yu, Jin-Quan. And the article was included in Chemical Science in 2013.Name: 6-Chloro-1-methylpyrazolo[5,4-b]pyridine This article mentions the following:

C3-arylated indazole and pyrazoles are privileged structural motifs in agrochems. and pharmaceuticals. C-3 C-H arylation of (1H) indazole and pyrazole was a significant challenge due to the poor reactivity of the C-3 position. Herein, the authors report a practical Pd(ii)/Phen catalyst and conditions for the direct C-3 arylation of indazole and pyrazole with ArI or ArBr without using Ag additives as halide scavengers. The use of toluene, chlorobenzene, trifluoromethylbenzene and mesitylene as the solvent is crucial for the selectivity and reactivity. The authors further demonstrate the robustness of this protocol through the first total synthesis of nigellidine hydrobromide as well as the expedient preparation of heterocycles structurally related to pesticides and drug mols. In the experiment, the researchers used many compounds, for example, 6-Chloro-1-methylpyrazolo[5,4-b]pyridine (cas: 63725-52-0Name: 6-Chloro-1-methylpyrazolo[5,4-b]pyridine).

6-Chloro-1-methylpyrazolo[5,4-b]pyridine (cas: 63725-52-0) belongs to pyrazole derivatives. Pyrazole is a weak base, with pKb 11.5 (pKa of the conjugated acid 2.49 at 25 °C).Pyrazole used as a ligand to prepare organometallic compounds. The presence of both electronegative nitrogen atoms in the pyrazole ring reduces the electron density of the C3- and C5-positions leaving electron density of C4-position unaltered. Thus the C4-position is vulnerable to electrophilic attack. The C3 electrophilic-position may undergo deprotonation in the presence of a strong base leading to ring opening.Name: 6-Chloro-1-methylpyrazolo[5,4-b]pyridine

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

High efficiency electroluminescence of orange-red iridium(III) complexes for OLEDs with an EQE over 30% was written by Su, Ning;Li, Shuaibing;Yang, Kun;Zhou, Feifan;Song, Jun;Zhou, Liang;Qu, Junle. And the article was included in Dyes and Pigments in 2021.Name: 2-(5-Methyl-1H-pyrazol-3-yl)pyridine This article mentions the following:

In this study, three pyrazol-pyridine ligands, 2-(3-methyl-1H-pyrazol-5-yl)pyridine (mepzpy), 2-(3-(trifluoromethyl)-1H-pyrazol-5-yl)pyridine (cf3pzpy), and 2-(3-phenyl-1H-pyrazol-5-yl)pyridine (phpzpy) were successfully synthesized for three orange-red iridium (III) complexes Ir₁, Ir₂, and Ir₃, resp., in which (2,6-bis(trifluoromethyl)pyridin-4-yl)isoquinoline (BTPIQ) was applied as main ligand. Their single crystals were obtained by vacuum sublimation. They showed distinct photoluminescent emissions at 583 nm with a shoulder peak at 624 nm, with high phosphorescence quantum yields of up to 89%. Organic light-emitting devices (OLEDs) with these complexes as emitters exhibits good performances. Especially, the device with Ir₃ complex achieves the best performance with a maximum luminance of 24,188 cd m^-2, and a highest external quantum efficiency of 30.65%. This research proved that Ir(III) complexes show highly enhanced performance by the modification of electro-donating benzene ring group into ancillary ligands, which also offers us an efficient strategy to obtain high efficiency orange-red Ir(III) complexes for OLEDs. In the experiment, the researchers used many compounds, for example, 2-(5-Methyl-1H-pyrazol-3-yl)pyridine (cas: 19959-77-4Name: 2-(5-Methyl-1H-pyrazol-3-yl)pyridine).

2-(5-Methyl-1H-pyrazol-3-yl)pyridine (cas: 19959-77-4) belongs to pyrazole derivatives. An alternative way to synthesize multisubstituted pyrazoles is the Csingle bondH arylation of simple pyrazoles. Pyrazoles and pyrimidines have diverse biological and pharmacological activities. There are a number of antimicrobial compounds containing pyrazole moiety as the core unit. Pyrazofurin is important antimicrobial drug and 2-methylpyrimidine-4-ylamine derivatives I and II were found to be effective inhibitors of Escherichia coli PDHc-E1 with antibacterial and antifungal activity.Name: 2-(5-Methyl-1H-pyrazol-3-yl)pyridine

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Evaluating hydrogen-bond propensity, hydrogen-bond coordination and hydrogen-bond energy as tools for predicting the outcome of attempted co-crystallisations was written by Sarkar, Nandini;Aakeroy, Christer B.. And the article was included in Supramolecular Chemistry in 2020.Safety of 4-Chloro-3,5-dimethyl-1H-pyrazole This article mentions the following:

Two different structure-informatics based methods and one approach based on hydrogen-bond interaction energies were evaluated for their abilities to predict the exptl. outcomes of attempted co-crystallisations between two known drug mols., Nevirapine and Diclofenac, and a series of potential co-formers. The hydrogen-bond propensity (HBP) tool gave the correct result in 26 out of 30 cases, whereas a hydrogen-bond coordination (HBC) method predicted the correct outcome in 22 out of 30 cases. Finally, calculated hydrogen-bond energies (HBE) using a simple electrostatic model, gave the correct result in 23 out of 30 experiments In those cases, where the crystal structure of a co-crystal of either Nevirapine or Diclofenac was known, we also examined how well the three methods predicted which primary hydrogen-bond interactions were present in the crystal structure. HBP correctly predicted 6 out of 6 cases, HBC could not predict any of the synthon formations correctly, and HBE successfully predicted 1 out of 6 cases. In the experiment, the researchers used many compounds, for example, 4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8Safety of 4-Chloro-3,5-dimethyl-1H-pyrazole).

4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8) belongs to pyrazole derivatives. Pyrazole is a weak base, with pKb 11.5 (pKa of the conjugated acid 2.49 at 25 °C).Pyrazole used as a ligand to prepare organometallic compounds. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, antidiabetic and antibacterial activities.Safety of 4-Chloro-3,5-dimethyl-1H-pyrazole

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Carbon-13 NMR chemical shifts of N-unsubstituted and N-methylpyrazole derivatives was written by Cabildo, Pilar;Claramunt, Rosa Maria. And the article was included in Organic Magnetic Resonance in 1984.Electric Literature of C5H7ClN2 This article mentions the following:

¹³C shielding data for 100 derivatives of pyrazole are reported. These include Me, Et, Pr, tert-Bu, Ph, hydroxymethyl, carboxyl, ethoxycarbonyl, cyano, amino, hydrazino, nitro, azido, chloro, bromo and iodo groups as substituents on the ring carbon atoms. In the experiment, the researchers used many compounds, for example, 4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8Electric Literature of C5H7ClN2).

4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8) belongs to pyrazole derivatives. The 1H-pyrazole provides an excellent means by which to provide the requisite hydrogen bond acceptor–donor motifs, whether as a monocyclic ring or as a fused indazole ring. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Electric Literature of C5H7ClN2

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

4-Nitro-5-(3-pyridyl)pyrazole, a new oxidation product of nicotine. III. Confirmatory synthetical experiments was written by Gough, Geo. A. C.;King, Harold. And the article was included in Journal of the Chemical Society in 1933.Application of 45887-08-9 This article mentions the following:

The by-product in the oxidation of nicotine to nicotinic acid, 4-nitro-5-(3-pyridyl)pyrazole (C. A. 26, 990), gives the 4-NH₂ derivative, which on deamination gives 3-(5-pyridyl)pyrazole (I), whose picrate, crystals with 1 H₂O, m. 194-5°, methiodide, m. 217.5°, methopicrate, m. 185°, flavianate, crystals with 2 H₂O, orange, m. 229° (decomposition). β-Pyridoylacetone and N₂H₄ give quant. 3-methyl-5-(3-pyridyl)pyrazole, crystals with 1.5 H₂O, m. 81-3°, and then 137-8°; picrate, m. 202-3°; HCl salt, m. 214-6°; oxidation with KMnO₄ gives 5-(3-pyridyl)pyrazole-3-carboxylic acid, m. 308-10° (decomposition); picrate, m. 242-5°; heating at 310° gives I. In the experiment, the researchers used many compounds, for example, 3-(1H-Pyrazol-3-yl)pyridine (cas: 45887-08-9Application of 45887-08-9).

3-(1H-Pyrazol-3-yl)pyridine (cas: 45887-08-9) belongs to pyrazole derivatives. As is the case with imidazoles, the pyrazole ring offers many opportunities to create new multiring systems that incorporate this heterocycle. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Application of 45887-08-9

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Expedited Palladium-Catalyzed Amination of Aryl Nonaflates through the Use of Microwave-Irradiation and Soluble Organic Amine Bases was written by Tundel, Rachel E.;Anderson, Kevin W.;Buchwald, Stephen L.. And the article was included in Journal of Organic Chemistry in 2006.Application of 3528-58-3 This article mentions the following:

Microwave-assisted, palladium-catalyzed C-N bond-forming reactions with aryl/heteroaryl nonaflates and amines using the soluble amine bases DBU or MTBD and ligands 2,4,6-(Me₂CH)₃C₆H₂C₆H₄PR₂-2 [R = cyclohexyl, CMe₃] and XantPhos resulted in good to excellent yields (71-99%) of arylamines in short reaction times (1-45 min). In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3Application of 3528-58-3).

1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3) belongs to pyrazole derivatives. The strategies for the synthesis of pyrazoles generally can be applied for the construction of indazoles. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Application of 3528-58-3

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Design, synthesis and anti-tuberculosis activity of 1-adamantyl-3-heteroaryl ureas with improved in vitro pharmacokinetic properties was written by North, E. Jeffrey;Scherman, Michael S.;Bruhn, David F.;Scarborough, Jerrod S.;Maddox, Marcus M.;Jones, Victoria;Grzegorzewicz, Anna;Yang, Lei;Hess, Tamara;Morisseau, Christophe;Jackson, Mary;McNeil, Michael R.;Lee, Richard E.. And the article was included in Bioorganic & Medicinal Chemistry in 2013.Application In Synthesis of 1-Ethyl-1H-pyrazol-3-amine This article mentions the following:

Out of the prominent global ailments, tuberculosis (TB) is still one of the leading causes of death worldwide due to infectious disease. Development of new drugs that shorten the current tuberculosis treatment time and have activity against drug resistant strains is of utmost importance. Towards these goals we have focused our efforts on developing novel anti-TB compounds with the general structure of 1-adamantyl-3-Ph urea. This series is active against Mycobacteria and previous lead compounds were found to inhibit the membrane transporter MmpL3, the protein responsible for mycolic acid transport across the plasma membrane. However, these compounds suffered from poor in vitro pharmacokinetic (PK) profiles and they have a similar structure/SAR to inhibitors of human soluble epoxide hydrolase (sEH) enzymes. Therefore, in this study the further optimization of this compound class was driven by three factors: (1) to increase selectivity for anti-TB activity over human sEH activity, (2) to optimize PK profiles including solubility and (3) to maintain target inhibition. A new series of 1-adamantyl-3-heteroaryl ureas was designed and synthesized replacing the Ph substituent of the original series with pyridines, pyrimidines, triazines, oxazoles, isoxazoles, oxadiazoles and pyrazoles. This study produced lead isoxazole, oxadiazole and pyrazole substituted adamantyl ureas with improved in vitro PK profiles, increased selectivity and good anti-TB potencies with sub μg/mL min. inhibitory concentrations In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-3-amine (cas: 55361-49-4Application In Synthesis of 1-Ethyl-1H-pyrazol-3-amine).

1-Ethyl-1H-pyrazol-3-amine (cas: 55361-49-4) belongs to pyrazole derivatives. Pyrazole is a weak base, with pKb 11.5 (pKa of the conjugated acid 2.49 at 25 °C).Pyrazole used as a ligand to prepare organometallic compounds. The presence of both electronegative nitrogen atoms in the pyrazole ring reduces the electron density of the C3- and C5-positions leaving electron density of C4-position unaltered. Thus the C4-position is vulnerable to electrophilic attack. The C3 electrophilic-position may undergo deprotonation in the presence of a strong base leading to ring opening.Application In Synthesis of 1-Ethyl-1H-pyrazol-3-amine

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Cu_1.5PMo₁₂O₄₀-catalyzed condensation cyclization for the synthesis of substituted pyrazoles was written by Yang, Guo-Ping;He, Xing;Yu, Bing;Hu, Chang-Wen. And the article was included in Applied Organometallic Chemistry in 2018.Safety of 4-Chloro-3,5-dimethyl-1H-pyrazole This article mentions the following:

A convenient and direct approach has been developed for the preparation of pyrazole derivatives by the condensation cyclization of hydrazines/hydrazide and 1,3-diketones in the presence of Cu₁.₅PMo₁₂O₄₀ (0.33 mol%) under mild conditions (r.t.-60°, 10-30 min). Notably, the reaction was found to be scalable as 99% yield was obtained when the reaction was performed at a 5-mmol scale. This solvent-free and halogen-free catalytic system represents an effective economic and environmentally friendly method for the construction of pyrazoles. In the experiment, the researchers used many compounds, for example, 4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8Safety of 4-Chloro-3,5-dimethyl-1H-pyrazole).

4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8) belongs to pyrazole derivatives. The strategies for the synthesis of pyrazoles generally can be applied for the construction of indazoles. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, antidiabetic and antibacterial activities.Safety of 4-Chloro-3,5-dimethyl-1H-pyrazole

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

5-Aminopyrazoles synthesis was written by Hoehn, Hans. And the article was included in Zeitschrift fuer Chemie in 1970.HPLC of Formula: 3528-58-3 This article mentions the following:

1-(R-Substituted)-5-aminopyrazoles and their 3-methyl and 4-methyl derivatives (57 compounds where R = aliphatic, cycloaliphatic, aralkyl, 2-furylmethyl, or 2-thienylmethyl) were prepared by treating CHR1:CR2CN (R1 = H, Me, etc., R2 = H, Me, Et) with N2H4 to give NH2NHCHR1CHR2CN, adding aldehyde or ketone R3R4CO to give R3CR4:NNHCHR1CHR2CN and treating the hydrazone with BuONa for 2-5 hr at 90-130°. In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3HPLC of Formula: 3528-58-3).

1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3) belongs to pyrazole derivatives. Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The pyrazole ring is resistant to oxidation and reduction but the groups, such as alkyl and formyl attached to the ring, are oxidized to respective acids. Only electrolytic oxidation, ozonolysis, and a strong base cause ring opening.HPLC of Formula: 3528-58-3

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Electrosynthesis of azopyrazoles via the oxidation of N-alkylaminopyrazoles on a NiO(OH) anode in aqueous alkali – A green method for N-N homocoupling was written by Lyalin, Boris V.;Sigacheva, Vera L.;Kokorekin, Vladimir A.;Petrosyan, Vladimir A.. And the article was included in Tetrahedron Letters in 2018.Name: 1-Ethyl-1H-pyrazol-3-amine This article mentions the following:

A nickel oxyhydroxide [NiO(OH)] anode was exploited to develop a new synthetic route for the electrocatalytic N-N homocoupling of N-alkylaminopyrazoles in an alk. aqueous medium. The advantages of this green electrochem. methodol. include low cost, atom economy and high yields. In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-3-amine (cas: 55361-49-4Name: 1-Ethyl-1H-pyrazol-3-amine).

1-Ethyl-1H-pyrazol-3-amine (cas: 55361-49-4) belongs to pyrazole derivatives. Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. Pyrazoles and pyrimidines have diverse biological and pharmacological activities. There are a number of antimicrobial compounds containing pyrazole moiety as the core unit. Pyrazofurin is important antimicrobial drug and 2-methylpyrimidine-4-ylamine derivatives I and II were found to be effective inhibitors of Escherichia coli PDHc-E1 with antibacterial and antifungal activity.Name: 1-Ethyl-1H-pyrazol-3-amine

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics