86-99-7Relevant articles and documents
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Cutler,Surrey
, p. 3394 (1950)
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Synthesis method of 4,7-dichloroquinoline
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Paragraph 0020; 0025-0026; 0029; 0034-0035; 0038; 0043-0044, (2020/07/15)
The invention discloses a synthesis method of 4,7-dichloroquinoline. The synthesis method is characterized by comprising the following steps: synthesizing 7-chloro-4-hydroxylquinoline-3-carboxylic acid by using a one-pot method, and carrying out decarboxylation and chlorination on the 7-chloro-4-hydroxylquinoline-3-carboxylic acid to obtain 4,7-dichloroquinoline. The step of synthesizing the 7-chloro-4-hydroxylquinoline-3-carboxylic acid by the one-pot method comprises the following sub-steps: with m-chloroaniline, triethyl orthoformate or trimethyl orthoformate and diethyl malonate as raw materials, carrying out condensation under the catalysis of anhydrous ferric trichloride to obtain diethyl 2-[[(3-chlorophenyl)amino]methylene]malonate, directly adding a condensation reaction solution into an organic solvent, carrying out heating cyclization to obtain 7-chloro-4-hydroxylquinoline-3-carboxylic acid ethyl ester, and after the cyclization reaction is completed, adding sodium hydroxidefor hydrolysis to obtain 7-chloro-4-hydroxylquinoline-3-carboxylic acid. Although the whole process comprises five reactions, intermediate products are good enough in purity and can be directly synthesized into a target product without purification, so operation is easy and convenient and industrialization is facilitated; and raw materials are easily available, and pollution is small.
Preparation method of hydroxychloroquine
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Paragraph 0114; 0125; 0127-0130, (2020/09/16)
The invention belongs to the technical field of medicine and chemical engineering, and particularly relates to a hydroxychloroquine preparation method. The method comprises: carrying out a condensation reaction on a quinoline intermediate 7-chloro-4-hydroxyquinoline sulfonate and a hydroxychloroquine side chain in a eutectic solvent to obtain a target product, wherein the preparation method of thequinoline intermediate 7-chloro-4-hydroxyquinoline sulfonate comprises the following steps: (1) by taking 4-chloro-2-nitrobenzoic acid as a raw material, carrying out a chlorination reaction to prepare acyl chloride, condensing the acyl chloride with Meldrum's acid, and hydrolyzing to obtain 4-chloro-2-nitroacetophenone; and (2) carrying out condensation reaction, nitro reduction cyclization andhydroxyl protection reaction on the 4-chloro-2-nitroacetophenone and N,N-dimethylformamide methylal to obtain the quinoline intermediate 7-chloro-4-hydroxyquinoline sulfonate. The method has the advantages of easily available raw materials, mild reaction conditions, difficulty in side reaction, avoidance of high-temperature production conditions, reduction of risks, good intermediate stability, high yield and good purity of the obtained hydroxychloroquine, and facilitation of large-scale production.
Synthesis, antituberculosis studies and biological evaluation of new quinoline derivatives carrying 1,2,4-oxadiazole moiety
Shruthi,Eswaran, Sumesh,Shivarudraiah, Prasad,Narayanan, Shridhar,Subramanian, Sangeetha
, p. 97 - 102 (2018/11/23)
Tuberculosis is the infectious disease caused by mycobacterium tuberculosis (Mtb), responsible for the utmost number of deaths annually across the world. Herein, twenty-one new substituted 1,2,4-oxadiazol-3-ylmethyl-piperazin-1-yl-quinoline derivatives were designed and synthesized through multistep synthesis followed by in vitro evaluation of their antitubercular potential against Mtb WT H37Rv. The compound QD-18 was found to be promising with MIC value of 0.5 μg/ml and QD-19 to QD-21 were also remarkable with MIC value of 0.25 μg/ml. Additionally, we have carried out experiments to confirm the metabolic stability, cytotoxicity and pharmacokinetics of these compounds along with kill kinetics of QD-18. These compounds were found to be orally bioavailable and highly effective. Altogether, these results indicate that QD-18, QD-19, QD-20 and QD-21 are promising lead compounds for the development of a novel chemical class of antitubercular drugs.