US 12,063,930 B2
Sulfonamide-containing 4-(N-methyl) aminopiperidine myricetin derivatives, preparation method and application
Wei Xue, Guiyang (CN); Shichun Jiang, Guiyang (CN); Ying Chen, Guiyang (CN); Shijun Su, Guiyang (CN); Jun He, Guiyang (CN); Mei Chen, Guiyang (CN); Meimei Jin, Guiyang (CN); Ming He, Guiyang (CN); and Jun Wang, Guiyang (CN)
Assigned to Guizhou University, Guiyan (CN)
Appl. No. 17/043,521
Filed by Guizhou University, Guiyang (CN)
PCT Filed Dec. 9, 2019, PCT No. PCT/CN2019/124090
§ 371(c)(1), (2) Date Sep. 29, 2020,
PCT Pub. No. WO2020/253152, PCT Pub. Date Dec. 24, 2020.
Claims priority of application No. 201910528656.3 (CN), filed on Jun. 18, 2019.
Prior Publication US 2023/0131193 A1, Apr. 27, 2023
Int. Cl. A61K 31/277 (2006.01); A01N 43/40 (2006.01); A01P 1/00 (2006.01); C07D 405/12 (2006.01)
CPC A01N 43/40 (2013.01) [A01P 1/00 (2021.08); C07D 405/12 (2013.01)] 1 Claim
 
1. A method of preparing 4-(N-methyl) aminopiperidine myricetin derivatives containing sulfonamide, the synthetic route of which is as follows: mixing myricetin with potassium carbonate (K2CO3) and N,N-dimethylformamide (DMF) and adding with methyl iodide (CH3I) to perform reaction, and followed by adding absolute ethyl alcohol (CH3CH2OH) to heat to reflux to obtain a clarified solution and adding concentrated hydrochloric acid (HCl) into the clarified solution under reflux, thereby
(1) obtaining 3-Hydroxy-3′,4′,5′,5,7-pentamethoxy myricetin (intermediate a)

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(2) combining the intermediate a with dibromoalkanes (Br(CH2)nBr) and potassium carbonate as a catalyst and DMF as a solvent for 1 day (d) at room temperature (rt) to obtain 3-bromo-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (intermediate b):

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(3) mixing the intermediate b and 4-(N-methyl) amino-N-Boc piperidine by taking potassium carbonate as a catalyst and acetonitrile as a solvent to prepare 3-(4-(N-methyl) amino-N-Boc piperidine)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one (intermediate c) under reflux and stirring at 80° C., wherein the Boc of intermediate c is a tert-butylcarbonyl protecting group:

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(4) removing the tert-butylcarbonyl (Boc) protecting group from the intermediate c with methanol (CH3OH) as a solvent and hydrochloride (HCl) at room temp (rt) for 2 hours (2h) to obtain hydrochloride (intermediate d) of the 3-(4-(N-methyl) aminopiperidine)-5,7-dimethoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromene-4-one

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(5) mixing the intermediate d and substituted sulfonyl chloride by taking potassium carbonate as a catalyst and absolute ethyl alcohol as a solvent to prepare the 4-(N-methyl) aminopiperidine myricetin derivatives containing sulfonamides (target compound I)

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