202197-26-0

Usage

Chemical Properties

Tan Solid

Uses

3-Chloro-4-(3-fluorobenzyloxy)aniline is an intermediate in the synthesis of Lapatinib (L175800).

InChI:InChI=1/C13H11ClFNO/c14-12-7-11(16)4-5-13(12)17-8-9-2-1-3-10(15)6-9/h1-7H,8,16H2

Upstream product

• 619-08-9 2-chloro-4-nitrophenol 
• 443882-99-3 3-chloro-4-(3-fluorobenzyloxy)nitrobenzene 
• 95-57-8 2-monochlorophenol 
• 3964-52-1 2-chloro 4-aminophenol 
• 456-41-7 1-(Bromomethyl)-3-fluorobenzene 
• 456-42-8 m-fluorobenzyl chloride 
• 456-47-3 3-fluoro-benzenemethanol 
• 350-30-1 3-chloro-4-fluoronitrobenzene 
• 878018-19-0 2-chloro-1-(3-fluoro-benzoyloxy)-4-nitro-benzene 

Downstream Products

• 231278-20-9 N-(3-chloro-4-(3-fluorobenzyloxy)phenyl)-6-iodoquinazolin-4-amine 
• 746677-53-2 N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-5-iodopyrimidin-4-amine 
• 859205-93-9 (S)-2-{4-[3-chloro-4-(3-fluoro-benzyloxy)-5 phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethoxy methyl}-morpholine-4-carboxylic acid tert-butyl ester 
• 859205-94-0 4-[3-chloro-4-(3-fluoro-benzyloxy)-phenylamino]-5-methyl-pyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid ethyl ester 
• 859205-97-3 [3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-(5-phenylsulfanylmethyl-pyrrolo[2,1-f][1,2,4]triazin-4-yl)-amine 
• 859206-10-3 thioacetic acid S-{4-[3-chloro-4-(3-fluoro-benzyloxy)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethyl} ester 
• 859205-92-8 {4-[3-chloro-4-(3-fluoro-benzyloxy)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-5-yl}-methanol 
• 892142-87-9 2-{[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]oxy}ethanol 
• 851545-72-7 [3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-(6-nitro-quinazolin-4-yl)-amine hydrochloride 
• 871025-24-0 N₄-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-iodopyrimidine-4,5-diamine 
• 871027-15-5 N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-5-(3-chloropropyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine 

Relevant academic research and scientific papers

Industrial Cunninghamia lanceolata carbon supported FeO(OH) nanoparticles-catalyzed hydrogenation of nitroarenes

The development of green and efficient methods for hydrogenation of nitroarenes is still highly demanding in organic synthesis. Herein, we report an industrial Cunninghamia lanceolata carbon supported FeO(OH) nanoparticles process for the synthesis of aryl amines with good yields via hydrogenation of nitroarenes. Nine key anti-cancer drug intermediates were successfully achieved with protocol. And Osimertinib intermediate 4m can be smoothly synthesized at a 2.67 kg-scale with >99.5% HPLC purity. This protocol features cheap carbon source, highly catalytic activity, simple operation, kilogram-scalable and recyclable catalysts (eight times without observable losing activity).

Discovery of novel and potent safinamide-based derivatives as highly selective hMAO-B inhibitors for treatment of Parkinson's disease (PD): Design, synthesis, in vitro, in vivo and in silico biological studies

Up to date, the current clinical practice employs only symptomatic treatments for management of Parkinson's disease (PD) but unable to stop disease progression. The discovery of new chemical entities endowed with potent and selective human monoamine oxidase B (hMAO-B) inhibitory activity is a clinically relevant subject. Herein, a structural optimization strategy for safinamide (a well-known second generation hMAO-B inhibitor) afforded a series of thirty-six safinamide-derived new analogs (4aa–bj). Most compounds showed promising inhibitory activities against hMAO-B (>70% inhibition at a single dose concentration of 10 μM), with no apparent effect on hMAO-A at 100 μM. Moreover, while six compounds (4ak, 4as, 4az, 4be, 4bg, and 4bi) exhibited potent double-digit nanomolar activities over hMAO-B with IC50 values of 29.5, 42.2, 22.3, 18.8, 42.2, and 33.9 nM, respectively, three derivatives (4aq, 4at, and 4bf), possessing the same carboxamide moiety (2-pyrazinyl), showed the most potent single-digit nanomolar activities (IC50 = 9.7, 5.1, and 3.9 nM, respectively). Compound 4bf revealed an excellent selectivity index (SI > 25641) with a 29-fold increase compared to safinamide (SI > 892). A structure activity relationship along with molecular docking simulations provided insights into enzyme ? inhibitor interactions and a rational for the observed activity. In an in vivo MPTP-induced mouse model of PD, oral administration of compound 4bf significantly protected nigrostriatal dopaminergic neurons as revealed by tyrosine hydroxylase staining and prevented MPTP-induced Parkinsonism as revealed by motor behavioral assays. Accordingly, we present compound 4bf as a novel, highly potent, and selective hMAO-B inhibitor with an effective therapeutic profile for relieving PD.

Catalytic production of anilines by nitro-compounds hydrogenation over highly recyclable platinum nanoparticles supported on halloysite nanotubes

Pt-nanoparticles supported on halloysite-nanotubes (HNTs) were selectively deposited onto the inner (Pt(IN)/HNT) or outer (Pt(OUT)/HNT) surface of the support to evaluate their operational stability on the cleaner and efficient hydrogenation of nitro compounds to produce their corresponding anilines. The formation of Pt0-aggregates on the inner or outer surfaces was observed, with mean particles sizes of 2.4–2.9 nm. The catalysts were evaluated using ethanol as solvent and nitrobenzene as a model substrate at a temperature of 298 K, under 1 bar of H2 pressure. The Pt(IN)/HNT catalyst showed better catalytic performance than Pt(OUT)/HNT, which was mainly attributed to the confinement effect of the Pt-nanoparticles inside the HNTs. However, the operational stability showed that Pt(OUT)/HNT retained its catalytic performance after 15 cycles, while the Pt(IN)/HNT catalyst suffered deactivation after the 5th cycle. The best catalytic system showed a moderate-to-high efficiency in the efficient hydrogenation of 7 nitro compounds used to produce their corresponding anilines, which are important pharmaceutical building blocks.

Targeting Her2-insYVMA with Covalent Inhibitors - A Focused Compound Screening and Structure-Based Design Approach

Mutated or amplified Her2 serves as a driver of non-small cell lung cancer or mediates resistance toward the inhibition of its family member epidermal growth factor receptor with small-molecule inhibitors. To date, small-molecule inhibitors targeting Her2 which can be used in clinical routine are lacking, and therefore, the development of novel inhibitors was undertaken. In this study, the well-established pyrrolopyrimidine scaffold was modified with structural motifs identified from a screening campaign with more than 1600 compounds, which were applied against wild-type Her2 and its mutant variant Her2-A775_G776insYVMA. The resulting inhibitors were designed to covalently target a reactive cysteine in the binding site of Her2 and were further optimized by means of structure-based drug design utilizing a set of obtained complex crystal structures. In addition, the analysis of binding kinetics and absorption, distribution, metabolism, and excretion parameters as well as mass spectrometry experiments and western blot analysis substantiated our approach.

HER2 Kinase-Targeted Breast Cancer Therapy: Design, Synthesis, and in Vitro and in Vivo Evaluation of Novel Lapatinib Congeners as Selective and Potent HER2 Inhibitors with Favorable Metabolic Stability

HER2 kinase as a well-established target for breast cancer (BC) therapy is associated with aggressive clinical outcomes; thus, herein we present structural optimization for HER2-selective targeting. HER2 profiling of the developed derivatives demonstrated

Promotional effect of palladium in Co-SiO2 core@shell nanocatalysts for selective liquid phase hydrogenation of chloronitroarenes

This study describes the synthesis of palladium-promoted Co@SiO2 catalyst developed by electrostatic immobilization of Pd ionic precursor onto Co3O4 nanoparticles core, coated with a mesoporous SiO2 shell. The oxidized Pd-Co3O4@SiO2 (xPdCo-ox) and partially reduced Pd-Co@SiO2 (xPdCo-red) nanocatalysts were used in the direct synthesis of chloro-arylamines from chloronitroarenes employing heterogeneous hydrogenation process. The effect of palladium content (xPdCo; x = 0.0, 0.5, 1.0 and 3.0 Pd wt%) in the Co3O4 core of the structures on catalytic performance for the hydrogenation of 4-chloronitrobenzene (CNB) to 4-chloroaniline (CAN) was systematically studied. It was found that the incorporation of palladium ionic precursor promotes both Co3O4 core nanoparticles flocculation and an increase in the mesoporous shell thickness in the Pd-promoted catalysts compared to the pristine Co-SiO2 core-shell structure. The TPR, XRD, XPS and magnetic measurements results indicated that the palladium addition promoted the reduction of Co3O4 core during the isothermal H2 treatment at 873 K rendering metallic Pd° and Co° species. The catalytic CNB hydrogenation experiments showed that the 0.5PdCo-red catalyst inhibited both the hydrodechlorination and intermediates accumulation reaching 99% yield in CAN compared to 1.0PdCo-red and 3.0PdCo-red catalysts which provided aniline as undesired product. Additionally, the 0.5PdCo-red catalyst was easily recycled with a moderate catalytic activity after five consecutive reaction cycles. Finally, the catalytic hydrogenation performance of the 0.5PdCo-red catalyst for different pharmaceutical substituted chloro-nitroarenes such as 1-(4-chlorophenoxy)-2-nitrobenzene, 2-chloro-1-((3-fluorobenzyl)oxy)-4-nitrobenzene and 2-chloro-5nitrobenzotrifluoride was also evaluated and revealed high activity (>99% at 3 h of reaction) and selectivity towards the desired chloro-arylmines production, highlighting the potential of this catalyst in these processes.

Pd-Co catalysts prepared from palladium-doped cobalt titanate precursors for chemoselective hydrogenation of halonitroarenes

Bimetallic Pd-Co catalysts supported on the mixed oxides CoTiO3-CoO-TiO2 (CTO) were synthesized via the thermal reduction of Pd-doped cobalt titanates PdxCo1-xTiO3 and evaluated for the chemoselective hydrogenation of halonitroarenes to haloarene-amines. The nominal Pd mass percentage of the Pd-Co/CTO systems was varied from 0.0 to 0.50. After the thermal reduction of PdxCo1-xTiO3 at 500 °C for 3 h, Pd was completely reduced and Co was partially reduced, producing a mixture of ionic Co, metallic Co, and TiO2-rutile species to give the supported bimetallic catalysts. The metallic cobalt content increased with the Pd content of the precursor. The catalytic activity toward 4-chloronitrobenzene increased with the Pd content; however, >0.1 mass% Pd decreased the chemoselectivity toward 4-chloroaniline due to the formation of the hydrodehalogenation product—aniline. The 0.1Pd-Co/CTO system was used as a model catalyst to produce haloarene-amine building blocks for linezolid, loxapine, lapatinib, and sorafenib with >98% conversion, 96% chemoselectivity, and no hydrohalogenation products. Finally, recycling tests of the 0.1Pd-Co/CTO catalyst showed loss of activity and selectivity during the third cycle due to catalyst deactivation. Regeneration treatments, every two catalytic cycles, allowed six operation cycles without loss of chemoselectivity and only a slight decrease in catalytic activity during the last cycle.

A process for preparing the lapatinib method and intermediate (by machine translation)

A through novel intermediate to prepare lapatinib or its pharmaceutically acceptable salt of the method, the method using 5 - bromo furfural and and 2 - nitrobenzene formic acid as the starting material through the Suzuki coupling reaction. This kind of synthetic pulls the handkerchief to raise nepal method can reach 32.2% overall yield. (by machine translation)

Method for synthesizing lapatinib intermediate in microchannel reactor

The invention provides a method for synthesizing a lapatinib intermediate in a microchannel reactor, and belongs to the field of anticancer drug synthesis in organic synthesis. The method solves the problems that in a traditional synthesis process of a hi

1,2-DITHIOLANE AND DITHIOL COMPOUNDS USEFUL IN TREATING MUTANT EGFR-MEDIATED DISEASES AND CONDITIONS

Compositions of the invention comprise 1,2-dithiolane, dithiol and related compounds useful as therapeutic agents for the treatment and prevention of diseases and conditions associated with aberrant EGFR activity.