877399-50-3

Usage

Uses

Used in Medicinal Chemistry:
4-(4-Bromopyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester is used as a key intermediate for the synthesis of pharmaceutical agents and drug candidates. Its unique structure and functional groups contribute to the development of new therapeutics with improved efficacy and selectivity.
Used in Heterocyclic Compounds Synthesis:
In the field of organic chemistry, 4-(4-Bromopyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester is utilized as a building block for the construction of various heterocyclic compounds. These heterocyclic compounds are often found in biologically active molecules and can be further modified for specific applications.
Used in Drug Discovery and Development:
4-(4-Bromopyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester is employed as a scaffold in drug discovery and development due to its unique reactivity and pharmacological properties. The bromopyrazole group allows for the attachment of various functional groups, enhancing the molecule's potential as a therapeutic agent.
Used in Pharmaceutical Industry:
4-(4-Bromopyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester is used as a precursor in the pharmaceutical industry for the production of innovative drugs. Its versatility in chemical modifications makes it a valuable component in the creation of new medications with targeted therapeutic effects.
Used in Chemical Research:
In the realm of chemical research, 4-(4-Bromopyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester serves as a model compound for studying the reactivity and properties of bromopyrazole and piperidine derivatives. This research can lead to a better understanding of the structure-activity relationships in medicinal chemistry and the development of more effective drugs.

InChI:InChI=1/C13H20BrN3O2/c1-13(2,3)19-12(18)16-6-4-11(5-7-16)17-9-10(14)8-15-17/h8-9,11H,4-7H2,1-3H3

Upstream product

• 2075-45-8 4-bromo-1H-pyrazole 
• 141699-59-4 1-(tert-butoxycarbonyl)piperidin-4-yl methanesulfonate 
• 877399-60-5 4-(4-bromo-1H-pyrazol-1-yl)piperidine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 118811-07-7 tert-butyl 4-(tosyloxy)piperidin-1-carboxylate 
• 5382-16-1 4-HYDROXYPIPERIDINE 
• 109384-19-2 t-butyl 4-hydroxy piperidine-1-carboxylate 

Downstream Products

• 1428476-86-1 4-(4-{6-amino-5-[(R)-1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-3-yl}-pyrazol-1-yl)-piperidine-1-carboxylic acid tert-butyl ester 
• 877399-60-5 4-(4-bromo-1H-pyrazol-1-yl)piperidine 
• 1076224-00-4 4-(4-formylpyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester 
• 877399-74-1 tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate 
• 1309961-03-2 4-(4-bromo-1H-pyrazol-1-yl)-1-ethylpiperidine 
• 1309960-75-5 N'-{3-[1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl]-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl}-N,N-dimethylsulfuric diamide 
• 877401-42-8 tert-butyl 4-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate 
• 1361058-63-0 tert-butyl 4-(4-cyano-1H-pyrazol-1-yl)piperidine-1-carboxylate 
• 1430727-71-1 tert-butyl 4-(4-(1-(5-acetamido-2',4'-difluorobiphenyl-3-yl)-1H-benzo[d]-imidazol-5-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate 
• 1430723-67-3 N-(2',4'-difluoro-5-(5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-1H-benzo[d]-imidazol-1-yl)biphenyl-3-yl)acetamide 
• 1430728-12-3 tert-butyl 4-(4-(1-(3-acetamido-5-(1H-pyrazol-1-yl)phenyl)-1H-benzo[d]imidazol-5-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate 
• 1430724-58-5 N-(3-(5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)-5-(1H-pyrazol-1-yl)phenyl)acetamide 
• 1430724-59-6 N-(3-(5-(1-(1-(methylsulfonyl)piperidin-4-yl)-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)-5-(1H-pyrazol-1-yl)phenyl)acetamide 
• 1430728-20-3 tert-butyl 4-(4-(3-(5-acetamido-2',4'-difluorobiphenyl-3-yl)-3H-imidazo[4,5-b]pyridin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate 

Relevant academic research and scientific papers

SUBSTITUTED PYRAZOLE COMPOUNDS AS TOLL RECEPTOR INHIBITORS

Disclosed are compounds of Formula (I) N-oxides, or salts thereof, wherein G, A, R1, and R5 are defined herein. Also disclosed are methods of using such compounds as inhibitors of signaling through Toll-like receptor 7, or 8, or 9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.

Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis

Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclinical investigation of 29d, a potent antitrypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments.

BIFUNCTIONAL DEGRADERS AND THEIR METHODS OF USE

Described herein are bifunctional degrader compounds, their various targets, their preparation, pharmaceutical compositions comprising them, and their use in the treatment of conditions, diseases, and disorders mediated by various target proteins.

Preparation method of tert-butyl 4-(4-halo-1H-pyrazol-1-yl)piperidin-1-carboxylate

The invention discloses a preparation method of a crizotinib intermediate tert-butyl 4-(4-halo-1H-pyrazol-1-yl)piperidin-1-carboxylate, and belongs to the field of synthesis of medical intermediates.Tert-butyl 4-hydroxypiperidin-1-carboxylate is used as a raw material, the raw material and 4-halogenated pyrazole undergo a Mitsunobu reaction in the presence of triphenylphosphine and azodicarboxylic acid derivatives, an acid is added to adjust the pH, an intermediate 4-(4-halo-1H-pyrazol-1-yl)piperidine hydrochloride is obtained, alkaline dissociation is carried out, and meanwhile, Boc protection is carried out so that the tert-butyl 4-(4-halo-1H-pyrazol-1-yl)piperidin-1-carboxylate is obtained. The method has the advantages of simple process, cheap and easily available raw materials, highreaction selectivity, avoidance of elimination of byproducts, and simple post-treatment. The recrystallized tert-butyl 4-(4-halo-1H-pyrazol-1-yl)piperidin-1-carboxylate of a crude product has high purity and yield of 98.5% or above.

Crizotinib intermediate, preparation method and crizotinib preparation method

The invention relates to a crizotinib intermediate, a preparation method and a crizotinib preparation method, in particular to an intermediate of crizotinib which has the structure of a formula (CZT-5) as shown in the description and the structure of a formula (CZT-9) as shown in the description, a preparation method of the intermediate and a preparation method of a crizotinib with the structure of a formula (CZT-11). The method provided by the invention has the characteristics of short route, high yield, easiness in acquisition of raw materials, high reaction selectivity and the like, chiral resolution is not required in a synthetic process, the utilization rate of the raw materials is increased, the path costs are low, and therefore, the method can meet requirements of large-scale industrial production.

Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine and 1H-pyrazolo[3,4-b]pyridine derivatives as c-Met inhibitors

Five novel 1H-pyrrolo[2,3-b]pyridine or 1H-pyrazolo[3,4-b]pyridine derivatives, with a methylene, sulfur, sulfoxide or cyclopropyl group as a linker, were designed, synthesized and biologically evaluated against c-Met and ALK. The development of these methods of compound synthesis may provide an important reference for the construction of novel 7-azaindole and 7-azaindazole derivatives with a single atom linker. The enzyme assay and cell assay in vitro showed that compound 9 displayed strong c-Met kinase inhibition with IC50 of 22.8 nM, moderate ALK kinase inhibition, and strong cell inhibition with MKN-45 IC50 of 329 nM and EBC-1 IC50 of 479 nM. In order to find the better candidate compounds, compounds 8, 9 and 10 have been selected as tool compounds for further optimization.

PROTEIN KINASE INHIBITORS

A compound of formula (I), wherein R3, R4, G, B, M, and Z are as defined in the claims, and pharmaceutically acceptable salts thereof are disclosed. The compounds of formula (I) possess utility as FGFR inhibitors and are useful in the treatment of a condition, where FGFR kinase inhibition is desired, such as cancer.

AMINOPYRIDINE DERIVATIVES AS TAM FAMILY KINASE INHIBITORS

Provided herein are aminopyridine derivatives and pharmaceutical compositions that are useful as TAM family kinase inhibitors.

A novel approach for the synthesis of Crizotinib through the key chiral alcohol intermediate by asymmetric hydrogenation using highly active Ir-Spiro-PAP catalyst

A novel approach for the synthesis of Crizotinib (1) is described. In addition, new efficient procedures have been developed for the preparation of (S)-1-(2,6-dichloro-3-fluorophenyl)ethanol (2) and tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl) piperidine-1-carboxylate (4), the key intermediates required for the synthesis of Crizotinib.

PROTEIN KINASE INHIBITORS

A compound of formula (I), wherein R3, R4, G, B, M, and Z are as defined in the claims, and pharmaceutically acceptable salts thereof are disclosed. The compounds of formula (I) possess utility as FGFR inhibitors and are useful in the treatment of a condition, where FGFR kinase inhibition is desired, such as cancer.