449758-17-2

Usage

Uses

Used in Pharmaceutical Industry:
1-(Tetrahydro-2H-pyran-2-yl)-1H-pyrazole is used as a key intermediate for the synthesis of pyrazoloisoindoles and other pyrazole derivatives, which are known for their diverse biological activities and potential therapeutic applications. These compounds can be further modified and optimized to develop new drugs with improved efficacy and safety profiles.
Used in Chemical Synthesis:
1-(Tetrahydro-2H-pyran-2-yl)-1H-pyrazole is used as a versatile building block in organic synthesis, allowing chemists to create a wide range of complex molecules with specific properties and functions. Its unique structure and reactivity make it an attractive candidate for the development of new materials, catalysts, and other specialty chemicals.
Used in Research and Development:
1-(Tetrahydro-2H-pyran-2-yl)-1H-pyrazole is used as a valuable research tool for studying the structure-activity relationships of pyrazole-containing compounds. Its synthesis and subsequent modification can provide insights into the design and optimization of new molecules with desired properties, such as improved pharmacokinetics, selectivity, and potency.

Upstream product

• 110-87-2 3,4-dihydro-2H-pyran 
• 288-13-1 NH-pyrazole 
• 142-68-7 TETRAHYDROPYRANE 
• 903550-26-5 1-tetrahydropyran-1H-pyrazolylboronic ester 
• 1357587-46-2 N-(3-bromo-2-fluorophenyl)-2,5-difluoro-N-(methoxymethyl)benzenesulfonamide 
• 848440-23-3 (3-bromo-2-fluorophenyl)carbamic acid tert-butyl ester 

Downstream Products

• 376584-63-3 1H-pyrazole-5-boronic acid 
• 1238062-44-6 5-benzyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazole 
• 1297537-35-9 2-Chloro-4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)benzonitrile 
• 1240521-52-1 tert-butyl (S)-1-(5-(1H-pyrazol-5-yl)pyridin-3-ylamino)-1-oxo-3-phenylpropan-2-ylcarbamate 
• 14521-80-3 3-bromo-1H-pyrazole 
• 1044270-96-3 3-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole 
• 2000-93-3 3-Amino-4-chlor-1-hexyl-benzol 
• 1279088-80-0 1-(tetrahydro-2H-pyran-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole 

Relevant academic research and scientific papers

Green protection of pyrazole, thermal isomerization and deprotection of tetrahydropyranylpyrazoles, and high-yield, one-pot synthesis of 3(5)-alkylpyrazoles

We report a new synthetic approach that opens up the possibility of large scale, one-pot pyrazole derivatization by a wide variety of functionalities, including alkyl, halogen, hydroxyl, amino, azido, carbonyl, and organo-element (e.g., B, Si, P) groups. The approach is illustrated by the highly efficient synthesis of fourteen 3(5)-alkylpyrazoles, including the novel isopentyl- and n-hexadecyl derivatives, as well as 1,6-bis(pyrazol-3(5)-yl)hexane. The value of the new approach lies in the discovery of a green (solvent- and catalyst-free, quantitative) protection of pyrazole, followed by a high-yield lithiation/alkylation/deprotection sequence in the same pot. For the first time, the corresponding N-tetrahydropyran-2-yl (THP) intermediates have been isolated and characterized. Thermal isomerization of the 5-alkyl-1-(THP) to the 3-alkyl-1-(THP) isomer is shown to be an advantageous, green alternative to the acid-catalyzed, sequential protecting-group switching methodology in pyrazole chemistry. The X-ray crystal structures of 1,6-bis(pyrazol-3(5)-yl)hexane and 5-n-hexadecyl-1-(tetrahydropyran-2-yl)pyrazole reveal supramolecular architectures that shine light on the remarkable affinity for water and unexpected insolubility in organic solvents of alkylene-bridged bis(pyrazoles). 3(5)-Alkylpyrazoles are obtained in high yield from pyrazole by a one-pot procedure.

Drastic Deprotonation Reactivity Difference of 3- and 5-Alkylpyrazole Isomers, Their I2-Catalyzed Thermal Isomerization, and Telescoping Synthesis of 3,5-Dialkylpyrazoles: The Adjacent Lone Pair Effect Demystified

N-Protected 3-alkylpyrazoles are easily deprotonated by nBuLi at the 5-position of the aromatic ring, while the 5-alkyl isomers are completely unreactive under the same conditions. Using computational analysis, we reveal that electron pair repulsion within the deprotonated anion is not the reason behind the lack of reactivity of 5-alkylpyrazoles. Instead, diminished π-resonance and attractive electrostatic interactions within the pyrazole ring are responsible for the observed effect. A greener, telescoping alternative to the synthesis of 3,5-dialkylpyrazoles is presented. (Chemical Equation Presented).

Decatungstate-Mediated C(sp3)–H Heteroarylation via Radical-Polar Crossover in Batch and Flow

Photocatalytic hydrogen atom transfer is a very powerful strategy for the regioselective C(sp3)–H functionalization of organic molecules. Herein, we report on the unprecedented combination of decatungstate hydrogen atom transfer photocatalysis with the oxidative radical–polar crossover concept to access the direct net-oxidative C(sp3)–H heteroarylation. The present methodology demonstrates a high functional group tolerance (40 examples) and is scalable when using continuous-flow reactor technology. The developed protocol is also amenable to the late-stage functionalization of biologically relevant molecules such as stanozolol, (?)-ambroxide, podophyllotoxin, and dideoxyribose.

Thiofunctionalization of Electron-Rich Heteroarenes through Magnesiation and Trapping with Octasulfur

Herein we report a site-selective and thiol-free thiofunctionalization of electron-rich heteroarenes. After a selective ortho-magnesiation, the use of S8 followed by an electrophile allows direct access to S-alkyl or -aryl derivatives. In situ oxidation provides the corresponding sulfoxide and sulfone derivatives. Applying this protocol, Cerlapirdine was prepared in 4 steps with 28% overall yield. (Figure presented.).

METHODS FOR THE PREPARATION OF 5-BROMO-2-(3-CHLORO-PYRIDIN-2-YL)-2H-PYRAZOLE-3-CARBOXYLIC ACID

Described herein are novel methods of synthesizing 5-Bromo-2-(3-chloro-pyridin-2-yl)- 2H-pyrazole-3-carboxylic acid from pyrazole or pyrazole derivatives.

HETEROCYCLIC COMPOUND, PHARMACEUTICAL COMPOSITION COMPRISING SAME, PREPARATION METHOD THEREFOR, AND USE THEREOF

The present invention relates to a heterocyclic compound, a pharmaceutical composition comprising same, a preparation method therefor, and a use thereof. Specifically, the compound of the present invention is represented by formula (I), and used for preventing or treating a disease or condition related to RET activity.

GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE

Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme glycolate oxidase (GO). Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.

A mild and efficient THP protection of indazoles and benzyl alcohols in water

A mild and efficient method for THP protection of indazoles and benzyl alcohols has been developed in water, the most environmentally friendly solvent, in which Tween 20 (2% w/w) was added to form aqueous micelles to increase the solubility of starting materials. This aqueous protocol allowed the reaction to proceed smoothly at room temperature and with only 1.2 equiv of DHP, providing moderate to good yields of THP protected products for a wide scope of substrates. In addition, the methodology was highly practical in the large-scale synthesis (1 g synthesis of 2c as an example), wherein the convenient work-up and purification procedure (simple filtration) made the protocol even more attractive.

Direct Alkenylation of Allylbenzenes via Chelation-Assisted C-C Bond Cleavage

A novel method for direct transformation of allyl groups in allylbenzene derivatives to alkenyl groups via rhodium-catalyzed C-C bond cleavage is reported. The alkenylation with styrenes of allylbenzenes containing pyridyl and pyrazolyl groups as a directing group proceeded efficiently to give alkenylation products. We also developed a new protocol for transformation of an ortho-prenylated phenol to an aniline derivative.

EPOTHILONE ANALOGS, METHODS OF SYNTHESIS, METHODS OF TREATMENT, AND DRUG CONJUGATES THEREOF

In one aspect, the present disclosure provides epothilone analogs of the formula (I) wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. Additionally, drug conjugates with cell targeting moieties of the compounds are also provided.