1428476-86-1

Basic information

• Product Name: (S)-tert-Butyl 4-(4-(6-aMino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate
• Synonyms: (S)-tert-Butyl 4-(4-(6-aMino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate
• CAS NO: 1428476-86-1
• Molecular Formula: C26H30Cl2FN5O3
• Molecular Weight: 550.4525032
• Mol File: 1428476-86-1.mol
• Article Data: 27

Chemical Properties

• Appearance: /
• CAS DataBase Reference: (S)-tert-Butyl 4-(4-(6-aMino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-tert-Butyl 4-(4-(6-aMino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate(1428476-86-1)
• EPA Substance Registry System: (S)-tert-Butyl 4-(4-(6-aMino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate(1428476-86-1)

Safety Data

• Hazardous Substances Data: 1428476-86-1(Hazardous Substances Data)

Usage

General Description

The chemical "(S)-tert-butyl 4-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate" is a complex compound with a piperidine core and multiple functional groups attached to it. The molecule contains a pyrazole ring, a pyridine ring, and a carboxylate group, as well as a tert-butyl group. The compound also contains an amine group and several halogen atoms, including chloro and fluoro substituents. This chemical structure suggests that it may have potential applications in pharmaceutical or agrochemical research, as it contains structural features commonly found in bioactive molecules. Additionally, the stereochemistry of the compound is specified with the (S)-configuration, which is important for understanding the reactivity and interactions of the molecule.

Upstream product

• 1448326-33-7 5-bromo-3-[1 (R)-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine 
• 74115-13-2 5-bromopyridine-3-ol 
• 691872-15-8 5-bromo-3-hydroxy-2-nitropyridine 
• 290835-85-7 2',6'-dichloro-3'-fluoroacetophenone 
• 1331786-34-5 (±)-bis(Boc)-3-(1-(2,6-dichloro-3-fluoropheny)ethoxy)-5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-2-amine 
• 1331786-33-4 (±)-bis(Boc)-5-bromo-3-(1-(2,6-dichloro-3-fluoropheny)ethoxy)pyridin-2-amine 
• 756503-69-2 (±)-5-bromo-3-(1-(2,6-dichloro-3-fluoropheny)ethoxy)pyridin-2-amine 
• 756520-67-9 (±)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine 
• 756521-08-1 (±)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-nitropyridine 
• 756520-66-8 1-(2,6-dichloro-3-fluorophenyl)ethanol 
• 877399-08-1 (±)-3-(1-(2,6-dichloro-3-fluoropheny)ethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine 
• 877399-50-3 4-(4-bromo-1H-pyrazol-1-yl)piperidine-1-carboxylic acid tert-butyl ester 
• 756509-08-7 3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1H-pyrazol-4-yl)pyridin-2-amine 
• 141699-59-4 1-(tert-butoxycarbonyl)piperidin-4-yl methanesulfonate 

Downstream Products

• 877399-52-5 crizotinib 
• 1428476-71-4 N-(3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(1-ethylpiperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)acetamide 
• 1428476-72-5 3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-N-ethyl-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine 
• 1428476-85-0 tert-butyl 4-(4-(5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-6-(ethylamino)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate 
• 1428476-87-2 tert-butyl 4-(4-(6-acetamido-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate 
• 1418026-91-1 (R)-tert-butyl 4-(4-(6-acetamido-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate 
• 1418026-92-2 (R)-N-(3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-yl)acetamide 

Relevant articles and documents

Synthesis of a Crizotinib Intermediate via Highly Efficient Catalytic Hydrogenation in Continuous Flow

Kilogram-scale highly selective catalytic hydrogenation of the aryl nitro group in the intermediate of crizotinib has been developed, which adopted continuous-flow technology with prepassivated Raney Ni as a catalyst at room temperature. According to the reaction condition optimization, side reactions such as dehalogenation, debenzylation, and reduction of other unsaturated functional groups were inhibited eminently. Moreover, catalytic hydrogenation of (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-nitropyridine (compound I) afforded the desired product (R)-3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-2-amine (compound II) with high selectivity (99.9%) and high conversion (99.5%). Finally, high-quality crizotinib was synthesized from intermediate II.

Development and biological investigations of hypoxia-sensitive prodrugs of the tyrosine kinase inhibitor crizotinib

Despite the huge success of tyrosine kinase inhibitors as anticancer agents, severe side effects are a major problem. In order to overcome this drawback, the first hypoxia-activatable 2-nitroimidazole-based prodrugs of the clinically approved ALK and c-MET inhibitor crizotinib were developed. The 2-aminopyridine functionality of crizotinib (essential for target kinase binding) was considered as ideal position for prodrug derivatization. Consequently, two different prodrugs were synthesized with the nitroimidazole unit attached to crizotinib either via carbamoylation (A) or alkylation (B) of the 2-aminopyridine moiety. The successful prodrug design could be proven by docking studies and a dramatically reduced ALK and c-MET kinase-inhibitory potential. Furthermore, the prodrugs showed high stability in serum and release of crizotinib in an enzymatic nitroreductase-based cleavage assay was observed for prodrug A. The in vitro activity of both prodrugs was investigated against ALK- and c-MET-dependent or –overexpressing cells, revealing a distinct hypoxia-dependent activation for prodrug A. Finally, inhibition of c-MET phosphorylation and cell proliferation could also be proven in vivo. In summary of the theoretical, chemical and biological studies, prodrug derivatization of the 2-aminopyridine position can be considered as a promising strategy to reduce the side effects and improve the anticancer activity of crizotinib.

Palladium removal method for crizotinib intermediate

The invention discloses a method for removing palladium from a crizotinib intermediate. The method comprises the following steps: adding a heavy metal ion remover into a palladium-containing reactionsolution; after the remover is separated, a solid is sep