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Chemical Structure| 86-98-6 Chemical Structure| 86-98-6
Chemical Structure| 86-98-6

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4,7-Dichloroquinoline is a quinoline derivative with good biological activity, widely used in the development of antimalarial, antibacterial, and antiviral drugs. Its dichloro substitution gives it unique pharmacological properties, making it a crucial intermediate for synthesizing quinoline-based drugs like chloroquine and quinolone antibiotics.

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Kitel, Radoslaw ; Surmiak, Ewa ; Borggrafe, Jan ; Kalinowska-Tluscik, Justyna ; Golik, Przemyslaw ; Czub, Miroslawa , et al.

Abstract: Here, we report the fragment-based drug discovery of potent and selective fragments that disrupt the Spire2-FMN2 but not the Spire1-FMN2 interaction. Hit fragments were identified in a differential scanning fluorimetry-based screen of an inhouse library of 755 compounds and subsequently validated in multiple orthogonal biophys. assays, including fluorescence polarization, microscale thermophoresis, and 1H-15N HSQC NMR. Extensive structure-activity relationships combined with mol. docking followed by chem. optimization led to the discovery of compound 13, which exhibits micromolar potency and high ligand efficiency (LE = 0.38). Therefore, this fragment represents a validated starting point for the future development of selective chem. probes targeting the Spire2-FMN2 interaction.

Greeshma P. Kumpati ; Michael J. Williams ; Srinidhi Mereddy ; Joseph L. Johnson ; Shirisha Jonnalagadda ;

Abstract: Several quinolino-benzoxaborole derivatives have been prepared to start from aminobenzoxaboroles. These derivatives have been evaluated for their anti-cancer activity on human and murine cancer cell lines and based on their relative non-toxicity, these compounds were further evaluated for their antibacterial activity against E. coli, B. subtilis, and M. smegmatis. The synthesized compounds were also evaluated for antifungal activity in C. albicans and C. neoformans.

Keywords: Benzoxaboroles ; Aminobenzoxaboroles ; Quinolino-Benzoxaboroles ; Anti-Microbial Agents

Purchased from AmBeed: ; ; ; ;

Kumpati, Greeshma P ;

Abstract: Benzoxaborole structure contains a phenyl ring fused with a heterocyclic oxaborole ring moiety. Benzoxaboroles are considerably more stable and exhibit high hydrolytic resistance compared with corresponding phenylboronic acids. The enhanced acidity of benzoxaboroles allows them to be predominantly in anionic forms in aqueous solution at physiological pH, which causes them to exhibit higher water solubility and better pharmacokinetic properties than phenylboronic acids. Increasing interest in benzoxaborole compounds is mainly due to their broad-spectrum biological activity including antimicrobial, anti-inflammatory and other medicinal properties. Quinoline is a highly privileged nitrogen containing a bicyclic ring system where a benzene ring is fused to a pyridine ring. The quinoline moiety is found in many natural products and has been traditionally used as a medicine for treating a wide variety of diseases. Quinoline-based molecules have been found to exhibit a diverse range of pharmacological properties with uses as antimalarial, antibacterial, anticonvulsant, cardiotonic, anticancer, anthelmintic, antifungal, anti-inflammatory and analgesic agents. In this regard, we envisioned that introduction of aminobenzoxaborole unit on quinolines would result in novel molecular entities with favorable pharmacological and pharmaceutical properties for developing therapeutic agents for a wide variety of diseases. The aims of the current work include: 1) Develop a new synthetic methodology for the rapid creation of aminobenzoxaborole containing quinolines; and 2) Explore the efficacy of synthesized candidate compounds as antibacterial, antifungal, antiviral, antiinflammatory, and antimalarial agents. As a part of this thesis, we developed a novel synthetic methodology for preparing quinolino aminobenzoxaboroles. The synthesized compounds were initially evaluated for their cytotoxic properties against various human and murine proliferating cancer cells. All the compounds were found to be well tolerated did not display toxicity even at high concentrations. Encouraged by their lack of toxicity, the test compounds were evaluated for their antibacterial activity against E. coli, B. subtilis, and M. smegmatis and for their antifungal activity against C. neoformans and C. albicans. Some of the synthesized derivatives exhibited good and selective activity against M. smegmatis. Future studies will involve evaluation of synthesized candidate compounds as antitubercular, antiviral, antimalarial, and anti-inflammatory agents.

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Alternative Products

Product Details of 4,7-Dichloroquinoline

CAS No. :86-98-6
Formula : C9H5Cl2N
M.W : 198.05
SMILES Code : C1=CC(=CC2=NC=CC(=C12)Cl)Cl
MDL No. :MFCD00006774
InChI Key :HXEWMTXDBOQQKO-UHFFFAOYSA-N
Pubchem ID :6866

Safety of 4,7-Dichloroquinoline

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of 4,7-Dichloroquinoline

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 86-98-6 ]

[ 86-98-6 ] Synthesis Path-Downstream   1~15

  • 1
  • [ 86-98-6 ]
  • [ 94050-90-5 ]
  • 2-{4-[(7-chloro-4-quinolinyl)oxy]phenoxy}propionic acid [ No CAS ]
  • 2
  • [ 86-98-6 ]
  • [ 255735-88-7 ]
  • [2-(7-chloroquinolin-4-ylamino)propyl]carbamic acid tert-butyl ester [ No CAS ]
  • 3
  • [ 86-98-6 ]
  • N,N,N-(ferrocenylmethyl)trimethylammonium iodide [ No CAS ]
  • [ 58966-93-1 ]
  • [ 830355-09-4 ]
  • [ 830355-10-7 ]
  • 4
  • [ 86-98-6 ]
  • [ 35613-44-6 ]
  • [ 25553-00-8 ]
YieldReaction ConditionsOperation in experiment
In acetonitrile; for 24h;Heating / reflux; A mixture of 160 g of 4,7-dichloroquinoline, 80 g of <strong>[35613-44-6]methyl 2-aminophenylacetate</strong> and 500 mL of acetonitrile is heated at reflux temperature for 24 hours. The solvent is evaporated under reduced pressure and the residue extracted 4 times with 750 mL portions of hot water. The aqueous extract is rendered basic (pH 8) with 10% ammonium hydroxide whereupon [2- (7-Chloro-quinolin-4-ylamino)-phenyl]-acetic acid methyl ester separates as an oil which crystallizes upon addition of ethanol. The product may be recrystallized from aqueous methanol, M.P.147-148C.[0114] The hydrochloride of £2-(7-Chloro-quinolin-4-ylamino)-phenyl]-acetic acid methyl ester may be prepared in conventional manner by treating a solution of the free base in ether with gaseous hydrochloric acid; M.P. 224-226C. [0115] To a solution of 6 g of [2-(7-Chloro-quinolin-4-ylamino)-phenyl]-acetic acid methyl ester in 100 mL of hot methanol is added 3 g of methanesulfonic acid. The solution is cooled to room temperature and 750 mL of ether is added. The product precipitates as off-white crystals and is collected by filtration. The resulting methanesulfonate of the above-mentioned compound is recrystallized from methanol-ether, M.P. 179-1810C.
  • 5
  • [ 1075-35-0 ]
  • [ 86-98-6 ]
  • [ 96-32-2 ]
  • [ 629644-21-9 ]
YieldReaction ConditionsOperation in experiment
5-Chloro-2-methylindole (0.16 g) and 4,8-dichloroquinoline (0.2 g) were suspended in NMP (0.5 ml) and heated in a microwave at [100W,] 140 C for 60 minutes. When reaction was complete THF (5 ml) was added followed by sodium hydride 60% dispersion in oil (0.12 g). After 30 mins a solution of methyl bromoacetate (0.2 ml) in THF [(1] ml) was added and the mixture stirred at room temperature for 24 hours. Ethyl acetate and saturated brine solution were added, the aqueous phase was separated and extracted with ethyl acetate. The combined organic solution was evaporated to leave a residue which was purified by silica gel chromatography using dichloromethane/ethyl acetate (9: 1) to provide the sub-title product as an oil. (120 mg). MS: APCI (+ve): 399/401/403 [[M+H] +]
  • 6
  • [ 86-98-6 ]
  • [ 22600-77-7 ]
  • [ 1404112-69-1 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; phenol; at 130℃; for 5h;Inert atmosphere; A mixture of <strong>[22600-77-7](1H-imidazol-2-yl)methanamine dihydrochloride</strong> 10 (27, 440 mg, 2.59 mmol), 4,7-dichloroquinoline (615 mg, 3.10 mmol), phenol (1.2 g, 13 mmol) and DIPEA (0.9 ml, 5.18 mmol) was heated for 5 h at 130 C, stirring under N2. After cooling, the mixture was diluted with CH2Cl2 and alkalized with 2 N NaOH until a precipitate was formed. The solid was filtered off, washed in succession with CH2Cl2, 2 N NaOH solution, water and dried overnight in vacuo (over KOH pellets).
  • 7
  • [ 86-98-6 ]
  • [ 526-08-9 ]
  • [ 1449365-38-1 ]
  • 8
  • [ 86-98-6 ]
  • [ 878799-20-3 ]
  • [ 1349530-48-8 ]
  • 9
  • [ 86-98-6 ]
  • [ 51387-92-9 ]
  • [ 69-44-3 ]
YieldReaction ConditionsOperation in experiment
85.69 g With sodium hydroxide; at 100℃; for 1h;pH 3.0; In the three-neck bottle 16.0g diethylamine, 40.0g deionized water, 30.0g acetaminophen and 6.6g paraformaldehyde, heating to 80 C, thermal insulation reaction 30 minutes, cooling to 40 C the following, by adding 48g37% after the hydrochloric acid, is heated to 104 C, thermal insulation reaction 2 hours, after the reaction, lowering the temperature to 38 C -42 C, dropwise NaOH solution, adjusted to pH 3.0, adding 4,7-chloroquinoline 36.2g, heating to 100 C, thermal insulation reaction 1 hour, after the reaction, cooling to 3 C -7 C, stirring crystallization 2 hours to 3 hours, filtered, to control the temperature to 60 C -70 C, vacuum ? - 0.080 MPa, drying 8 hours to obtain Amodiaquine hydrochloride 85.69g, yield 92.89%, purity of 99.96%.
  • 10
  • [ 86-98-6 ]
  • [ 6398-87-4 ]
  • [ 1079041-41-0 ]
YieldReaction ConditionsOperation in experiment
98% A mixture of the amine 4 (2.75 mmol), and 4,7-dichloroquinoline 5 (2.5 mmol) in ethanol (10.0 mL) washeated under reflux for 3 h. After cooling, HCl 37% (0.5 mL) wasadded and the solution was stirred at room temperature for 5 min.The solid formed was filtered and washed with ethanol. 4.2.3.1. 3-((7-Chloroquinolin-4-yl)amino)benzaldehyde 6.Beige solid; 98% yield; m.p. 195-197 C. FTIR (ATR) ν (cm-1): 3443(NH), 3069 (C-H), 2897 (-(C=O)-H), 1700 (C=O). 1H NMR(400 MHz, DMSO-d6) δ ppm 6.90 (d, J = 7.0 Hz, 1H, H3), 7.80 (t,J = 7.7 Hz, 1H, Hm), 7.83-7.90 (m, 2H, H6, Ho), 7.96 (d, J = 7.4 Hz, 1H,Hp), 8.01 (s, 1H, Ho’), 8.22 (d, J = 2.0 Hz, 1H, H8), 8.56 (d, J = 7.0 Hz,1H, H2), 8.96 (d, J = 9.2 Hz, 1H, H5), 10.08 (s, 1H, CHO), 11.44 (s, 1H,NH). 13C NMR (100 MHz, DMSO-d6) δ ppm 100.5,116.2,119.2,125.5,126.4, 127.5, 128.5, 130.9, 131.1, 137.6, 138.0, 138.5, 139.0, 143.6,154.8, 192.6. MS (70 eV) m/z (%): 282/284 [M+] (100/32), 281 (52),253 (60), 218 (58), 190 (17).
  • 11
  • [ 86-98-6 ]
  • [ 80041-89-0 ]
  • 4,7-dichloro-2-isopropylquinoline [ No CAS ]
  • 12
  • [ 86-98-6 ]
  • [ 29608-05-7 ]
  • 7-chloro-N-(4-(piperidino-1-ylmethyl)phenyl)quinolin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With hydrogenchloride; In ethanol;Reflux; General procedure: To a solution of 4,7-dichloroquinoline (1mmol, 1.2 equiv.) in ethanol (20mL) was added concentrated hydrochloric acid (catalytic amount from one to two drops) and stirred by 4min. To this mixture was added the corresponding aniline 3a-e (1 equiv.) and stirred under reflux for 4h. During the reaction a yellow precipitate was observed, the mixture was then cooled to room temperature and the precipitated solid filtered, washed with ethanol and dried under reduced pressure to yield the desired quinolines 4a-e.
  • 13
  • [ 86-98-6 ]
  • [ 16803-92-2 ]
  • N-(4-chlorophenyl)-4-((7-chloroquinolin-4-yl)amino)benzenesulfonamide hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% General procedure: A mixture of 0.001 mol of compound (41a-d or 45), 1 equivalentof the respective 4-amino-N-arylbenzenesulfonamides (44a-g) and3 mL of ethanol was stirred and refluxed (78 C) for 2 h. The reactionmixture was poured into ice water, and the precipitateformed was vacuum filtered and washed with water. The precipitatewas purified by recrystallization from methanol/water (2:1) orchromatography TLC Glass Plates (Merck TLC Silica gel 60 RP-18F254s) in chloroform/methanol (9.5:0.5). After purification, therespective hydrochloride was prepared, and the molecules weresolubilized and stirred for 15 min in a 1:1 solution of HCl/H2O andconcentrated under vacuum [17e19].
  • 14
  • [ 86-98-6 ]
  • [ 263162-13-6 ]
  • C19H27ClN4O2 [ No CAS ]
  • 15
  • [ 86-98-6 ]
  • [ 157837-31-5 ]
  • 7-chloro-N-[3-(oxazol-5-yl)phenyl]quinolin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
87.33% With indium(III) chloride; In acetonitrile; at 110 - 170℃;Microwave irradiation; General procedure: To a solution of 3-aminobiphenyl derivatives with appropriate substituted group of 4-chloroquinoline in 10-15mL acetonitrile, and added indium (III) chloride as the catalyst in the Glass vial, followed by placing in the microwave reactor. Microwave wattage was between 300 and 900W, heating at 110C to 170C for 30min to 3h. After the completion of reaction, the mixture was concentrated under vacuum and then subjected to purify by flash chromatography with different proportion of dichloromethane/methanol. The solid was recrystallized in acetonitrile and filtered to obtained the desired compound.
87.33% With indium(III) chloride; In acetonitrile; at 110 - 170℃;Microwave irradiation; General procedure: To a solution of 3-aminobiphenyl derivatives with appropriate substituted group of 4-chloroquinoline in 10-15mL acetonitrile, and added indium (III) chloride as the catalyst in the Glass vial, followed by placing in the microwave reactor. Microwave wattage was between 300 and 900W, heating at 110C to 170C for 30min to 3h. After the completion of reaction, the mixture was concentrated under vacuum and then subjected to purify by flash chromatography with different proportion of dichloromethane/methanol. The solid was recrystallized in acetonitrile and filtered to obtained the desired compound.
 

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