67459-52-3Relevant articles and documents
Optically active chloroquine and hydroxychloroquine and analogues thereof, and preparation method, composition and application of optically active chloroquine and hydroxychloroquine
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Paragraph 0297; 0301-0303; 0317; 0321-0323, (2021/03/11)
The invention provides a rapid and simple method for preparing optically active chloroquine, hydroxychloroquine and analogues thereof, which comprises the following steps: reacting racemates of chloroquine, hydroxychloroquine and analogues thereof with an acidic chiral resolution reagent to generate corresponding salts, and separating and purifying to obtain optically pure salts of chloroquine, hydroxychloroquine and analogues thereof, and reacting with alkali to obtain (R)- or (S)- chloroquine with high optical purity and (R)- or (S)- hydroxychloroquine and analogues thereof. The method is simple and convenient to operate and low in cost, the enantiomer purity can reach 99.9% ee, and industrial production of chloroquine, hydroxychloroquine and analogues thereof with single chiral configuration is easy to realize. The invention also provides (R)- or (S)- chloroquine and (R)- or (S)- hydroxychloroquine and analogues thereof, pharmaceutical compositions and uses thereof, optically activechloroquine and hydroxychloroquine and analogues thereof reduce toxic and side effects, and have better treatment effects on coronavirus, influenza virus and autoimmune diseases.
Preparation method of enantiomer pure chloroquine and chloroquine phosphate
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Paragraph 0047; 0051, (2021/01/29)
The invention discloses a preparation method of enantiomer pure chloroquine and chloroquine phosphate, which comprises the following steps of: salifying racemic 2-amino-5-diethylaminopentane under theaction of single-configuration acid to form diastereomer salt, separating out the diastereomer salt from the solution to obtain single-configuration 2-amino- 5-diethylaminopentane intermediate salt,and the like. According to the method, racemic 2-amino- 5-diethylaminopentane is salified under the action of single-configuration acid to form diastereomer salt. On the basis of synthesizing chloroquine/chloroquine phosphate in the prior art, 2-amino-5-diethylaminopentane is used as a raw material to form diastereomer salt to resolve chiral raw materials. The method is high in purity, green and suitable for large-scale production, hazardous chemicals do not need to be introduced, salifying resolution is achieved, reaction energy barriers are reduced through catalyst application, the reactionrate is increased, side reactions are reduced, the optical purity of the product is improved through HPLC determination, the resolution cost is reduced, and the method is suitable for large-scale production.
Chloroquine phosphate enantiomer crystal form and preparation method thereof
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Paragraph 0029, (2020/10/14)
The invention discloses a chloroquine phosphate enantiomer crystal form and a preparation method thereof. The invention provides (R)/(S)-chloroquine phosphate and a preparation method thereof. According to the (S)-chloroquine phosphate provided by the invention, an X-ray powder diffraction pattern expressed by a 2theta angle has characteristic peaks at 10.4 degrees, 10.7 degrees, 15.6 degrees, 15.8 degrees, 17.8 degrees, 18.9 degrees, 21.3 degrees and 23.9 degrees +/-0.2 degrees. According to the (R)-chloroquine phosphate provided by the invention, an X-ray powder diffraction pattern expressedby a 2theta angle has characteristic peaks at 10.3 degrees, 15.5 degrees, 15.7 degrees, 17.8 degrees and 18.8 degrees +/-0.2 degrees.