A kind of synthetic method of 3-bromo-7-hydroxyquinoline

A synthetic method, the technology of hydroxyquinoline, applied in the direction of organic chemistry, etc., can solve the problems of low total yield of 3-bromo-7-hydroxyquinoline, few synthesis reports, high toxicity, etc., and achieve simple synthesis route, easy operation Convenient post-processing and high total yield

Active Publication Date: 2021-05-04
SUZHOU KANGRUN PHARMA
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  • Claims
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Problems solved by technology

3-Bromo-7-hydroxyquinoline, as a pharmaceutical intermediate of a new type of PRMT5 inhibitor, has attracted attention by using it as an intermediate to synthesize some specific compounds to obtain highly effective drug candidate molecules, and has attracted widespread attention in the field of medicinal chemistry. attention, but there are few synthetic reports related to it
But in this technique, raw material dichlorodicyanobenzoquinone (DDQ) meets water and decomposes very easily, emits hydrogen cyanide, has high toxicity; And the overall yield of this technique 3-bromo-7-hydroxyquinoline is lower

Method used

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  • A kind of synthetic method of 3-bromo-7-hydroxyquinoline

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Experimental program
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Embodiment

[0033]First step: Synthesis of quinolin-7-trifluoromethanesulfonate

[0034]7-hydroxyquinoline (100 g, 0.69 mol) was added to dichloromethane (800 mL), and pyridine (140 g, 1,77 mol) was added at 0 ° C, and trifluoromethanesulfonic anhydride (230 g, 0.83 mol) was added dropwise. Dichloromethane (200 mL) solution, after completion of the reaction for 2 h. After the reaction, the reaction solution was poured into ice water (500 mL), and the pH to 6-7 was adjusted with HCl, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated to obtain quinoline-7-trifluoromethanesulfonic acid. Ester (150 g, 78.6%).

[0035]Step 2: Synthesis of 3-Brominin-7-trifluoromethanesulfonate

[0036]Under 90 ° C, quinolin-7-trifluoromethanesulfonate (40 g, 0.14 mol) was added to Icevene (800 mL), and N-Bromoimide (38 g, 0.22 mol) was added batch. ), Reaction 2h. After the reaction is complete, the cyclic acetic acid is extracted with ethyl acetate (500 ml * 2), and the organic phase is campe...

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Abstract

The invention provides a method for synthesizing 3-bromo-7-hydroxyquinoline. The synthesis method of 3-bromo-7-hydroxyquinoline of the present invention comprises the following steps: 1) dissolving 7-hydroxyquinoline in a solvent, adding trifluoromethanesulfonic anhydride, and reacting at low temperature to obtain quinoline-7-trifluoroquinoline mesylate, wherein the molar ratio of the 7-hydroxyquinoline to the trifluoromethanesulfonic anhydride is 1:(1~1.5); 2) the quinoline-7-trifluoroform obtained in step 1) The sulfonate is dissolved in a solvent, and N-bromosuccinimide is added to obtain 3-bromoquinoline-7-trifluoromethanesulfonate after the reaction; 3) the 3-bromoquinoline-7-trifluoromethanesulfonate obtained in step 2) Hydrolysis of the 7-triflate under basic conditions affords 3-bromo-7-hydroxyquinoline. The synthesis method of 3-bromo-7-hydroxyquinoline of the present invention has stable raw materials, non-toxicity, simple synthesis process and high yield.

Description

Technical field[0001]The invention belongs to the technical field of drug intermediate synthesis, and is relate to a synthesis method of 3-bromo-7-hydroxyquinoline.Background technique[0002]3-bromo-7-hydroxyquinoline is a pharmaceutical intermediate having a significant drug value, and Janssen Pharmaceuticanv researchers have found that a series of compounds synthesized in 3-bromo-7-hydroxyquinoline are highly efficient PRMT5 inhibition. The agent, PRMT5 is one of the main methyltransferases responsible for arginine monohydrogenation and symmetry dimethylbacte, which is involved in various cells by apparently regulating the expression of target gene expression or signal molecules. process. The focus is, although PRMT5 is considered to be clinically relevant drug targets, but the selected PRMT5 inhibitor has little (WO2017032840A1).[0003]Therefore, the market has a strong demand for new PRMT5 inhibitors to create a new way for cancer treatment or prevention. 3-bromo-7-hydroxyquinolin...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D215/20
CPCC07D215/20
Inventor 黄家慧徐卫良徐炜政
Owner SUZHOU KANGRUN PHARMA
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