367-22-6

Usage

Uses

Used in Pharmaceutical Industry:
4-Chloro-3-fluoroaniline is used as a key intermediate in the synthesis of Methyl 5-Chloro-4-fluoro-1H-indole-2-carboxylate. 4-Chloro-3-fluoroaniline serves as a precursor to phosphoindole inhibitors, which are crucial in the development of treatments for HIV by targeting the non-nucleoside reverse transcriptase enzyme.
Additionally, 4-Chloro-3-fluoroaniline is utilized in the synthesis of 3-Deschloro-4-desfluoro-4-chloro-3-fluoro Gefitinib (D289540), which is an impurity of the tyrosine kinase inhibitor Gefitinib. Gefitinib is a medication used in the treatment of certain types of cancer, particularly non-small cell lung cancer. The synthesis of this impurity helps in the purification and quality control of Gefitinib, ensuring the safety and efficacy of the drug for patients.

InChI:InChI=1/C6H5ClFN/c7-5-2-1-4(9)3-6(5)8/h1-3H,9H2

Upstream product

• 351-31-5 N-(4-chloro-3-fluorophenyl)acetamide 
• 2268-05-5 1,3-dichloro-2-fluorobenzene 
• 277301-97-0 2,2-dimethyl-N-(4-chloro-3-fluorophenyl)propanamide 
• 106-47-8 4-chloro-aniline 
• 351-28-0 N-(3-fluorophenyl)acetamide 
• 372-19-0 meta-fluoroaniline 
• 869299-68-3 1,1-dimethylethyl (4-chloro-3-fluorophenyl)carbamate 
• 202982-67-0 1-chloro-2-fluoro-4-iodo-benzene 
• 16197-70-9 1-Chlor-2-fluor-4-benzoylamino-benzol 

Downstream Products

• 350-31-2 1-chloro-2-fluoro-4-nitrobenzene 
• 348-59-4 1,4-dichloro-2-fluorobenzene 
• 348-60-7 4-chloro-3-fluorophenol 
• 869299-68-3 1,1-dimethylethyl (4-chloro-3-fluorophenyl)carbamate 
• 937816-85-8 1-(2-amino-5-chloro-4-fluorophenyl)ethanone 
• 709-09-1 3,4-dimethoxynitrobenzene 
• 331-41-9 2-(4-chloro-3-fluorophenoxy)acetic acid 
• 788136-89-0 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl acetate 
• 247565-75-9 ethyl 2-(2-(2,4-difluorophenyl)hydrazono)propanoate 
• 473258-18-3 Ethyl pyruvate 4-chloro-3-fluorophenylhydrazone 
• 1097107-44-2 N-(4-Chloro-3-fluoro-phenyl)-methanesulfonamide 
• 1097107-46-4 N-(4-Chloro-3-fluoro-phenyl)-benzenesulfonamide 
• 1094759-93-9 4-chloro-5-fluoro-2-iodo-phenylamine 
• 1052114-96-1 N-(4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(4-chloro-3-fluorophenyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide 

Relevant academic research and scientific papers

Catalyst-Controlled Regioselective Chlorination of Phenols and Anilines through a Lewis Basic Selenoether Catalyst

We report a highly efficient ortho-selective electrophilic chlorination of phenols utilizing a Lewis basic selenoether catalyst. The selenoether catalyst resulted in comparable selectivities to our previously reported bis-thiourea ortho-selective catalyst, with a catalyst loading as low as 1%. The new catalytic system also allowed us to extend this chemistry to obtain excellent ortho-selectivities for unprotected anilines. The selectivities of this reaction are up to >20:1 ortho/para, while the innate selectivities for phenols and anilines are approximately 1:4 ortho/para. A series of preliminary studies revealed that the substrates require a hydrogen-bonding moiety for selectivity.

Direct Hydrogenation of a Broad Range of Amides under Base-free Conditions using an Efficient and Selective Ruthenium(II) Pincer Catalyst

The ruthenium(II) complex, [fac-PNHN]RuH(η1-BH4)(CO) (B; PNHN=8-(2-diphenylphosphinoethyl)aminotrihydroquinoline), is a highly versatile and effective catalyst (loadings of 0.1–1 mol %) for the hydrogenation of a multitude of amides, which include primary, secondary, and tertiary amides, to give their corresponding alcohols and amines in high yields under base-free conditions. All products were confirmed by using GC and GC–MS.

CD4 mimics as HIV entry inhibitors: Lead optimization studies of the aromatic substituents

Several CD4 mimics have been reported as HIV-1 entry inhibitors that can intervene in the interaction between a viral envelope glycoprotein gp120 and a cell surface protein CD4. Our previous SAR studies led to a finding of a highly potent analogue 3 with bulky hydrophobic groups on a piperidine moiety. In the present study, the aromatic ring of 3 was modified systematically in an attempt to improve its antiviral activity and CD4 mimicry which induces the conformational changes in gp120 that can render the envelope more sensitive to neutralizing antibodies. Biological assays of the synthetic compounds revealed that the introduction of a fluorine group as a meta-substituent of the aromatic ring caused an increase of anti-HIV activity and an enhancement of a CD4 mimicry, and led to a novel compound 13a that showed twice as potent anti-HIV activity compared to 3 and a substantial increase in a CD4 mimicry even at lower concentrations.

Copper(I)-catalyzed amination of aryl halides in liquid ammonia

The amination of aryl halides in liquid ammonia (LNH3) is catalyzed by a copper(I) salt/ascorbate system to yield primary aromatic amines in good to excellent yields. The low concentrations of catalyst required and the ease of product isolation suggest that this process has potential industrial applications. Commonly used ligands for analogous metal-catalyzed reactions are not effective. The rate of amination of iodobenzene in liquid ammonia is first order in copper(I) catalyst concentration. The small Hammett I? = 0.49 for the amination of 4-substituted iodobenzenes in liquid ammonia at 25 °C indicates that the C-I bond is not significantly broken in the transition state structure and that there is a small generation of negative charge in the aryl ring, which is compatible with the oxidative addition of the copper ion being rate limiting.

Robust synthesis of methyl 5-chloro-4-fluoro-1 h -indole-2-carboxylate: A key intermediate in the preparation of an HIV NNRTI candidate

A synthetic preparation of methyl 5-chloro-4-fluoro-1H-indole-2- carboxylate, a key intermediate towards phosphoindole inhibitors of HIV non-nucleoside reverse transcriptase, is described. The five-step synthesis involved Boc protection of the commercially available 4-chloro-3-fluoroaniline and regioselective iodination at C-2. After facile Boc deprotection, cyclization of the resultant o-iodoaniline gave the corresponding 5-chloro-4-fluoro-indole- 2-carboxylic acid which was subsequently esterified to provide the target indole ester in 56% overall yield. Identification of 6-chloro-7-iodo-2(3H)- benzoxazolone as a significant side product in the iodination step led to the development of conditions which eliminated its formation in subsequent batches. Advantages of this alternative approach relative to existing methodologies include (1) potentially hazardous diazonium and azido species were not required, (2) regioisomeric products were not generated, and (3) chromatographic isolations were avoided, as all intermediates were easily crystallized. As a result, the key indole ester was produced rapidly at 100-fold increased scale compared to previous reports with a 10-fold improvement in overall yield.

Novel ORL1-selective antagonists with oral bioavailability and brain penetrability

Following the discovery of 5-chloro-6-[piperazin-1-yl]-1H-benzimidazole as a novel pharmacophore for potent and selective ORL1 antagonist activity, optimization of this new lead by introduction of a methyl substitution on the piperazine ring resulted in a highly potent and selective, orally available, and brain penetrable ORL1 antagonist, 2-(tert-butylthio)-5-chloro-6-[(2R)-4-(2-hydroxyethyl)-2-methylpiperazin-1-yl]-1H-benzimidazole. Stereochemistry of the methyl substituent on the piperazine ring to control the functional activity of other opioid receptors is also described.

Electrophilic aromatic fluorination with fluorine: meta-Directed fluorination of anilines

Anilines are mainly or selectively fluorinated in the meta-position with F2 when dissolved in triflic acid, sometimes in the presence of small quantities of antimony pentafluoride. The regioselectivity is increased when an electron-donating substituent is present at the para-position.

BENZIMIDAZOLE DERIVATIVES

This invention relates to the compounds represented by a general formula [I]: ???[in which A1 and A2 represent optionally fluorine-substituted methine or the like; B represents halogen, cyano, lower alkyl or the like; D represents optionally substituted heterocyclic group or the like; and G represents C3-C20 aliphatic group such as alicyclic group]. These compounds inhibit nociceptin activities due to their high affinity to nociceptin receptor, and are useful as analgesic, antiobestic, corebral function improver, drugs for treatment of alzheimer's disease and dementia, remedies for schizophrenia and neurodegenerative diseases, antidepressant, remedies for diabetes insipidus, polyuria, hypotension and so on.

Benzimidazole derivatives

This invention provides compounds which are represented by a general formula [I] [in which X stands for hydrogen or halogen; B stands for halogen, cyano or optionally fluorine-substituted lower alkyl; D stands for a 3-10 membered aliphatic nitrogen-containing heterocyclic group; R3, R4 and R5 may be same or different, and each stands for hydrogen, lower alkyl optionally having substituent group(s) and the like; and a is 0 or 1]. These compounds exhibit high affinity to nociceptin receptors and whereby inhibit actions of nociceptin, and are useful as an analgesic, antiobestic, agent for ameliorating brain function, treating agents for Alzheimer's disease and dementia, and therapeutic agents for schizophrenia, neurodegenerative diseases, depression, diabetes insipidus, polyuria, hypotension and the like.