68817-71-0

Usage

Uses

Used in Pharmaceutical Synthesis:
2-AMINO-4'-CHLORODIPHENYLAMINE is used as a reagent in the synthesis of clofazimine analogs, which are employed as antileishmanials and antiplasmodials. These analogs are valuable in the treatment of leishmaniasis and malaria, respectively, due to their antimicrobial properties.
Used in Dye Production:
In the dye industry, 2-AMINO-4'-CHLORODIPHENYLAMINE is utilized in the preparation of N-(p-chloro)phenylbenzimidazolin-2-one and monoaminophenazine dyes. These dyes are known for their colorfastness and are used in various applications, including textiles, plastics, and printing inks, to impart vibrant and long-lasting colors.
Overall, 2-AMINO-4'-CHLORODIPHENYLAMINE is a versatile compound with applications in both the pharmaceutical and dye industries, highlighting its importance in the development of new drugs and colorants.

InChI:InChI=1/C12H11ClN2/c13-9-5-7-10(8-6-9)15-12-4-2-1-3-11(12)14/h1-8,15H,14H2

Upstream product

• 23008-56-2 N-(4-chlorophenyl)-2-nitroaniline 
• 99503-78-3 o-semidine 
• 88-73-3 2-Chloronitrobenzene 
• 953-14-0 N,N'-bis(4-chlorophenyl)hydrazine 
• 106-47-8 4-chloro-aniline 
• 1493-27-2 ortho-nitrofluorobenzene 
• 96762-04-8 3-amino-10-(4-chlorophenyl)-2-(4-chlorophenylimino)-2,10-dihydrophenazine 

Downstream Products

• 1137-69-5 2-chlorophenazine 
• 23698-43-3 N-(5-Chloro-2,4-dinitro-phenyl)-N'-(4-chloro-phenyl)-benzene-1,2-diamine 
• 81684-75-5 8-(4-chlorophenyl)naphtho<1',2':5,6>pyrano<2,3-b><1,5>benzodiazepin-15-(8H)one 
• 81684-79-9 13-(4-chlorophenyl)naphtho<1',2':5,6>pyrano<2,3-b><1,5>benzodiazepin-15-(13H)one 
• 64992-08-1 1,1'-Bis(4-chlorphenyl)-3,3'-dimethyl-1,1',2,2'-tetrahydro-2,2'-aethandiylidendichinoxalin 
• 74769-98-5 1-(4-Chlorphenyl)-3-phenyl-1H-chinoxalin-2-on 
• 95630-69-6 1-(4-Chlorphenyl)-2-<2-(4-chlorphenylamino)phenylamino>-2-methyl-3-phenyl-1,2-dihydrochinoxalin 
• 112069-70-2 10-(4'-Chlorophenyl)isoalloxazine 
• 32567-14-9 2,3-dianilino-5-(4-chloro-phenyl)-phenazinium-betaine 
• 90690-85-0 2-(4-chloranilino)-3,5-dihydro-5-(4-chlorphenyl)-3-iminophenazine hydrochloride 
• 175712-71-7 1,2-bis(4-chlorophenyl)-1H-benzo[d]imidazole 
• 24784-42-7 1-(4-chlorophenyl)-2-(4-methoxyphenyl)-benzimidazole 
• 930593-48-9 1-(4-chlorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide 

Relevant academic research and scientific papers

Design, synthesis, and biological evaluation of benzo[d]imidazole-2-carboxamides as new anti-TB agents

Tuberculosis is the leading cause of death globally among infectious diseases. Due to the development of resistance of Mycobacterium tuberculosis to currently used anti-TB medicines and the TB-HIV synergism the urgent need to develop novel anti-mycobacterial agents has been realized. The drug-to-target path has been the successful strategy for new anti-TB drug development. All the six drug candidates that have shown promise during the clinical trials and some of these being approved for treatment against MDR TB are the results of phenotype screening of small molecule compound libraries. In search of compounds belonging to novel pharmacophoric class that could be subjected to whole cell assay to generate new anti-TB leads the benzo[d]imidazole-2-carboxamide moiety has been designed as a novel anti-TB scaffold. The design was based on the identification of the benzimidazole ring as a prominent substructure of the FDA approved drugs, the structural analysis of reported anti-TB benzimidazoles, and the presence of the C-2 carboxamido functionality in novel bioisoteric anti-TB benzothiazoles. Twenty seven final compounds have been prepared via NH4Cl-catalyzed amidation of ethyl benzo[d]imidazole-2-carboxylates, as the required intermediates, obtained through a green “all water” one-pot synthetic route following a tandem N-arylation-reduction-cyclocondensation procedure. All of the synthesised target compounds were assessed for anti-TB potential using H37Rv ATCC27294 strain. Thirteen compounds were found with better MIC (0.78–6.25 μg/mL) than the standard drugs and being non-cytotoxic nature ( 60) and a few others e.g., 8a, 8f, 8k and 8o are the next best anti-TB hits (MIC: 1.56 μg/mL). The determination and analysis of various physiochemical parameters revealed favorable druglike properties of the active compounds. The compounds 8a-l and 8o, with MIC values of ≤ 6.25 μg/mL, have high LipE values (10.66–11.77) that are higher than that of the suggested value of > 6 derived from empirical evidence for quality drug candidates and highlight their therapeutic potential. The highest LipE value of 11.77 of the best active compound 8e with the MIC of 0.78 μg/mL indicates its better absorption and clearance as a probable clinical candidate for anti-TB drug discovery. These findings highlight the discovery of benzimidazole-2-carboxamides for further development as new anti-TB agents.

A green and practical reduction of N-(4-chlorophenyl)-2-nitroaniline and its derivatives to corresponding N-substituted-benzene-1,2-diamines using thiourea dioxide

A new effective approach for synthesizing diverse N-substituted-benzene-1,2-diamines is reported. The treatment of N-substituted-2-nitroanilines with thiourea dioxide in the presence of sodium hydroxide efficiently formed the corresponding N-substituted-benzene-1,2-diamines, including N-(4-chlorophenyl)benzene-1,2-diamine with a good yield of 94%. The by-product is environmentally-friendly urea and is easy to separate from the product by filtration procedure that enhances the convenience of the approach.

Design, synthesis and biological evaluation of novel 4-phenoxypyridine based 3-oxo-3,4-dihydroquinoxaline-2-carboxamide derivatives as potential c-Met kinase inhibitors

Blocking c-Met kinase activity by small-molecule inhibitors has been identified as a promising approach for the treatment of cancers. Herein, we described the design, synthesis, and biological evaluation of a series of 4-phenoxypyridine-based 3-oxo-3,4-dihydroquinoxaline derivatives as c-Met kinase inhibitors. Inhibitory activitives against c-Met kinase evaluation indicated that most of compounds showed excellent c-Met kinase activity in vitro, and IC50 values of ten compounds (23a, 23e, 23f, 23l, 23r, 23s, 23v, 23w, 23x and 23y) were less than 10.00 nM. Notably, three of them (23v, 23w and 23y) showed remarkable potency with IC50 values of 2.31 nM, 1.91 nM and 2.44 nM, respectively, and thus they were more potent than positive control drug foretinib (c-Met, IC50 = 2.53 nM). Cytotoxic evaluation indicated the most promising compound 23w showed remarkable cytotoxicity against A549, H460 and HT-29 cell lines with IC50 values of 1.57 μM, 0.94 μM and 0.65 μM, respectively. Furthermore, the acridine orange/ethidium bromide (AO/EB) staining, cell apoptosis assays by flow cytometry, wound-healing assays and transwell migration assays on HT-29 and/or A549 cells of 23w were performed. Especially compound 23w, which displayed potent antitumor, apoptosis induction and antimetastatic activity, could be used as a promising lead for further development. Meanwhile, their preliminary structure-activity relationships (SARs) were also discussed.

Clofazimine and intermediate preparation method

The present invention discloses a 3 - amino - 10 - (4 - chlorophenyl) - 2 (4 - chlorophenyl imine) - 2 - 10 - dihydro phenazino as raw materials for under acidic conditions, in the 30 - 50 °C lower reaction 36 - 96 hours to obtain 2 - amino - 4' - chloro-aniline, its self condensation reaction, to obtain N, 5 - double-(4 - chlorophenyl) - 3 - imino - 3, 5 - dihydro phenazine - 2 - amine, with isopropylamine reaction generating clofazimine. The method of the invention can be recycled in the industrialization process generating a large amount of waste of the 3 - amino - 10 - (4 - chlorophenyl) - 2 (4 - chlorophenyl imine) - 2 - 10 - dihydro phenazine, avoids the waste of the original material, not only can greatly reduce the production cost, also can be the development of the cycle production, in order to save resources and the purpose of environmental protection.

Design, synthesis and biological evaluation of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety as c-Met kinase inhibitors

A series of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety were synthesized and evaluated for their c-Met kinase inhibitory activity and antiproliferative activity against five cancer cell lines (HT-29, H460, A549, MKN-45 and U87MG) in vitro. Most of the compounds exhibited moderate-to-significant cytotoxicity as compared with foretinib. The most promising compound 41 (with c-Met IC50 value of 0.90?nM) showed remarkable cytotoxicity against HT-29, H460, A549, MKN-45 and U87MG cell lines with IC50 values of 0.06?μM, 0.05?μM, 0.18?μM, 0.023?μM and 0.66?μM, respectively, and thus it was 1.22- to 3.50-fold more potent than foretinib. Their preliminary structure-activity relationships (SARs) studies indicate that electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity.

Design, synthesis and antifungal activity of novel fenfuram-diarylamine hybrids

Ten novel fenfuram-diarylamine hybrids were designed and synthesized. And their antifungal activities against four phytopathogenic fungi have been evaluated in vitro and most of the compounds demonstrated a significant antifungal activities against Rhizoctonia solani and Sclerotinia sclerotiorum. Compound 5e exhibited the most potent antifungal activity against R. solani with an EC50value of 0.037 mg/L, far superior to the commercially available fungicide boscalid (EC50= 1.71 mg/L) and lead fungicide fenfuram (EC50= 6.18 mg/L). Furthermore, scanning electron microscopy images showed that the mycelia on treated media grew abnormally with tenuous, wizened and overlapping colonies compared to the negative control. Molecular docking studies revealed that compound 5e featured a higher affinity for succinate dehydrogenase (SDH) than fenfuram. Furthermore, it was shown that the 3-chlorophenyl group in compound 5e formed a CH-π interaction with B/Trp-206 and a Cl-π interaction with D/Tyr-128, rendering compound 5e more active than fenfuram against SDH.

Synthesis and biological evaluation of novel pyrazole carboxamide with diarylamine-modi?ed scaffold as potent antifungal agents

Twenty-seven novel pyrazole carboxamides with diarylamine-modi?ed scaffold were designed, synthesized and characterized in detail via 1H NMR, 13C NMR, IR and ESI-HRMS. Preliminary bioassays showed that some of the target compounds exhibited good antifungal activity against Rhizoctonia solani, Rhizoctonia cerealis and Sclerotinia sclerotiorum. Among them, compound 9c-7 exhibited the highest antifungal activities against R. solani, R. cerealis and S. sclerotiorum in vitro with IC50 values of 0.013, 1.608 and 1.874?μg/mL, respectively. Notably, compound 9c-7 still presented the highest fungicidal activities against R. solani in vivo with an IC50 value of 22.21?μg/mL. Molecular docking simulation results reveal that compound 9c-7 binds well to the hydrophobic pockets of the receptor protein succinate dehydrogenase. This study suggests that compound 9c-7 could act as a potential fungicide to be used for further optimization.

Method for synthesizing N-(4-chlorphenyl)-1,2-phenylenediamine as key clofazimine intermediate

The invention provides a method for synthesizing N-(4-chlorphenyl)-1,2-phenylenediamine as a key clofazimine intermediate. The method specifically comprises the following steps: 1) by taking o-fluoronitrobenzene and p-chloroaniline as raw materials and utilizing organic base as a catalyst for condensation reaction, reacting in an organic solvent and performing conventional treatment after ending the reaction, thereby acquiring a condensation intermediate N-(4-chlorphenyl)-2-nitryl-1-aniline; 2) by utilizing metallic nickel as the catalyst, performing catalytic hydrogenation reaction on the acquired condensation intermediate in the organic solvent and performing conventional treatment after reducing, thereby acquiring a rough product of N-(4-chlorphenyl)-1,2-phenylenediamine; and 3) re-crystallizing the acquired rough product with the organic solvent, thereby acquiring the end product.

Selective Hydrogenation of Halogenated Nitroaromatics to Haloanilines in Batch and Flow

The selective hydrogenation of functionalized nitroaromatics poses a major challenge from both academic as well as industrial viewpoints. As part of the CHEM21 initiative (www.chem21.eu), we are interested in highly selective, catalytic hydrogenations of halogenated nitroaromatics. Initially, the catalytic reduction of 1-iodo-4-nitrobenzene to 4-iodoaniline served as a model system to investigate commercial heterogeneous catalysts. After determining optimal hydrogenation conditions and profiling performances of the best catalysts, hydrogenations were transferred from batch to continuous flow. Finally, the optimized flow conditions were applied to transformations which represent important steps in the syntheses of the active pharmaceutical ingredients clofazimine and vismodegib.

Discovery of Benzotriazolo[4,3-d][1,4]diazepines as Orally Active Inhibitors of BET Bromodomains

Inhibition of the bromodomains of the BET family, of which BRD4 is a member, has been shown to decrease myc and interleukin (IL) 6 in vivo, markers that are of therapeutic relevance to cancer and inflammatory disease, respectively. Herein we report substituted benzo[b]isoxazolo[4,5-d]azepines and benzotriazolo[4,3-d][1,4]diazepines as fragment-derived novel inhibitors of the bromodomain of BRD4. Compounds from these series were potent and selective in cells, and subsequent optimization of microsomal stability yielded representatives that demonstrated dose- and time-dependent reduction of plasma IL-6 in mice.