443882-99-3

Basic information

• Product Name: 3-Chloro-4-(3-fluorobenzyloxy)nitrobenzene
• Synonyms: 3-Chloro-4-(3-fluorobenzyloxy)nitrobenzene;2-Chloro-1-(3-fluoro-benzyloxy)-4-nitrobenzene;1-(3-fluorobenzyloxy)-2-chloro-4-nitrobenzene;Benzene,2-chloro-1-[(3-fluorophenyl)Methoxy]-4-nitro-;1-Fluoro-3-[(4-nitro-2-chlorophenoxy)Methyl]benzene;4-(3-Fluorobenzyloxy)-3-chloronitrobenzene;2-Chloro-1-(3-fluoro-benzyloxy)-4-nitro-;Lapatinib genotoxic impurity 2
• CAS NO: 443882-99-3
• Molecular Formula: C₁₃H₉ClFNO₃
• Molecular Weight: 281.67
• Mol File: 443882-99-3.mol

Chemical Properties

• Melting Point: 99.0 to 103.0 °C
• Boiling Point: 400.5 °C at 760 mmHg
• Flash Point: 196 °C
• Appearance: /
• Density: 1.393 g/cm³
• Vapor Pressure: 2.92E-06mmHg at 25°C
• Refractive Index: 1.596
• Storage Temp.: Sealed in dry,Room Temperature
• CAS DataBase Reference: 3-Chloro-4-(3-fluorobenzyloxy)nitrobenzene(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Chloro-4-(3-fluorobenzyloxy)nitrobenzene(443882-99-3)
• EPA Substance Registry System: 3-Chloro-4-(3-fluorobenzyloxy)nitrobenzene(443882-99-3)

Safety Data

• Hazardous Substances Data: 443882-99-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3-Chloro-4-(3-fluorobenzyloxy)nitrobenzene is used as a key intermediate in the synthesis of novel indole-2-carboxamide derivatives, which are known for their anti-inflammatory properties. These derivatives are particularly useful in the treatment of sepsis, a life-threatening condition characterized by the body's extreme response to infection.
Additionally, 3-Chloro-4-(3-fluorobenzyloxy)nitrobenzene plays a significant role in the production of Niraparib (N481400), a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor. Niraparib has demonstrated efficacy in treating BRCA-1 and -2 mutant tumors, which are associated with an increased risk of developing breast and ovarian cancers. By inhibiting PARP enzymes, Niraparib helps to prevent the repair of damaged DNA in cancer cells, ultimately leading to their death.

InChI:InChI=1/C13H9ClFNO3/c14-12-7-11(16(17)18)4-5-13(12)19-8-9-2-1-3-10(15)6-9/h1-7H,8H2

Upstream product

• 619-08-9 2-chloro-4-nitrophenol 
• 456-47-3 3-fluoro-benzenemethanol 
• 350-30-1 3-chloro-4-fluoronitrobenzene 
• 456-41-7 1-(Bromomethyl)-3-fluorobenzene 
• 456-42-8 m-fluorobenzyl chloride 
• 99-54-7 3,4-dichloronitrobenzene 

Downstream Products

• 878018-21-4 4-{N-(3-chloro-4-(3-fluoro-benzyloxy)phenylamino)}-5,8-dihydro-6H-benzo[4,5]thieno[2,3-d]pyrimidin-7-one 
• 878014-52-9 2-[6-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-4,5-dihydro-3H-pyrimido[5',4':4,5]thieno[2,3-e]indazol-3-yl]ethanol 
• 552294-86-7 6-bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)thieno[2,3-d]pyrimidin-4-amine 
• 1152131-71-9 5-{4-[3-chloro-4-(3-fluorobenzyloxy)phenylamino]quinazolin-6-yl}thiophene-2-carbaldehyde 
• 1152132-00-7 5-{4-[3-chloro-4-(3-fluorobenzyloxy)phenylamino]quinazolin-6-yl}thiophene-2-carboxylic acid hydroxyamide hydrochloride 
• 1152131-99-1 5-{4-[3-chloro-4-(3-fluorobenzyloxy)phenylamino]quinazolin-6-yl}furan-2-carboxylic acid hydroxyamide hydrochloride 
• 1152131-95-7 3-[5-{4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl}furan-2-yl]-N-hydroxyacrylamide hydrochloride 
• 1152131-91-3 (E)-N-(2-aminophenyl)-3-(5-(4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl)furan-2-yl)acrylamide 
• 1152131-90-2 5-{4-[3-chloro-4-(3-fluorobenzyloxy)phenylamino]quinazolin-6-yl}thiophene-2-carboxylic acid (2-aminophenyl)amide 
• 1152131-89-9 5-{4-[3-chloro-4-(3-fluorobenzyloxy)phenylamino]quinazolin-6-yl}furan-2-carboxylic acid (2-aminophenyl)amide 
• 1152131-88-8 5-{4-[3-chloro-4-(3-fluorobenzyloxy)phenylamino]quinazolin-6-yl}thiophene-2-carboxylic acid (tetrahydropyran-2-yloxy)amide 
• 1152131-87-7 5-{4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)quinazolin-6-yl}furan-2-carboxylic acid (tetrahydropyran-2-yloxy)amide 

Relevant articles and documents

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.

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

Discovery of anilino-furo[2,3-d]pyrimidine derivatives as dual inhibitors of EGFR/HER2 tyrosine kinase and their anticancer activity

Being responsible for the development of many cancer types, EGFR (Epidermal Growth Factor Receptor) and HER2 (Human Epidermal growth factor Receptor 2) were the focus of this study where a series of novel 4-anilino-furo[2,3-d]pyrimidine derivatives was designed, synthesized and biologically evaluated. Modification of the solvent accessible 5-position side chain greatly affected the in-vitro EGFR/HER2 inhibitory activity. Three derivatives bearing 5-carboxylic acid side chain, namely the 3-chloroanilino derivative (8c), the 3-bromoaniline (8d) and the lapatinib analogue (10) demonstrated the most significant submicromolar EGFR inhibition. Surprisingly, the in-vitro assay of the ester 7h and its acid analogue 10 showed a significant variation of results between the antiproliferative activity against A549 cell line (IC50 0.5 and 21.4 μM) respectively and EGFR inhibitory activity (18% and 100%) respectively, suggesting that 7h might be a prodrug for 10. This assumption was also affirmed by the in-vivo results, where the in-vivo antitumor assessment against EAC (Ehrlich Ascites Carcinoma) solid tumor model revealed that 7h and 8d (10 mg/kg dose) exhibited antitumor activity comparable to that of gefitinib at the same dose, exhibiting TGI% of 67%, 71% and 70%, respectively. This effect could be explained, at least partly, via activation of apoptosis, where 7h and 8d caused more than 2-fold increase of caspase 3 and cytochrome c expression than the control group which is comparable to that of gefitinib-treated group. Finally, 7h was the most effective apoptotic inducer, resulting in a significant elevation in annexin V–FITC-positive apoptotic cells (both early and late apoptosis) by 25 and 79-folds, respectively, compared to control, which is higher than that of gefitinib (22 and 61-folds, respectively).

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

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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.

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Synthesis method of 3-chloro-4-(3-fluorobenzoyl)nitrobenzene

The invention discloses a synthesis method of 3-chloro-4-(3-fluorobenzoyl)nitrobenzene. According to the method, tributyl phosphine and tetramethylazodicarbonamide are used as catalysts, and 2-chloro-4-nitrophenol and 3-fluorobenzyl alcohol react to generate the 3-chloro-4-(3-fluorobenzoyl)nitrobenzene. According to the method disclosed by the invention, the synthesis yield is improved, and the utilization of m-fluorobenzyl bromide is avoided, so that the synthesis method is suitable for industrial production.

QUINAZOLINE DERIVATIVE, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION AND APPLICATION THEREOF

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