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A method for preparing 5-methyl-3-bromomethylpyridine hydrobromide

A technology of bromomethylpyridine bromate and hydrobromide, applied in the preparation of 5-methyl-3-bromomethylpyridine hydrobromide, pharmaceutical intermediate 5-methyl-3-bromomethylpyridine In the field of hydrobromide, it can solve the problems of low yield and complicated preparation process, and achieve the effect of simple reaction, simple post-treatment, and cheap and easy-to-obtain raw materials

Inactive Publication Date: 2016-08-24
SHANGHAI INST OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] For the defects existing in the above-mentioned prior art, the technical problem to be solved by this invention is to provide a kind of method for preparing 5-methyl-3-bromomethylpyridine hydrobromide, and this preparation method described will solve the present problem. There are technical problems in the preparation method in the art that the process is complicated and the yield is low

Method used

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  • A method for preparing 5-methyl-3-bromomethylpyridine hydrobromide
  • A method for preparing 5-methyl-3-bromomethylpyridine hydrobromide
  • A method for preparing 5-methyl-3-bromomethylpyridine hydrobromide

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Experimental program
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Embodiment 1

[0036] Synthesis of compound (3):

[0037]

[0038] In a 1000mL four-neck flask, add compound (2) 5-methylnicotinic acid (100.0g, 0.73mol) and 500mL methanol, and under nitrogen protection, add thionyl chloride (110mL, 1.5mol) dropwise, and keep the temperature at 20-25°C. After the dropwise addition, heat to reflux for 4 hours, remove methanol by evaporating under reduced pressure, add 200mL of ice water, neutralize to weakly alkaline (pH 7~10) with saturated sodium carbonate solution, extract with ethyl acetate, and use saturated brine for the organic phase After washing, drying over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure to obtain a white solid (108.2 g, 98.2%).

[0039] Melting Point: 44.9-45.4℃. MS(ESI, M+H) + : 151.95. 1 H NMR (400Hz, CDCl 3 ) δ 9.03(1H, s), 8.60(1H, s), 8.11(1H, s), 3.95(3H, s), 2.40(3H, s). IR(KBr, cm -1 for C 8 h 9 NO 2 : C:63.56; H: 6.00; N: 9.27. Found: C:63.57; H: 6.01; N: 9,30.

[0040] Synthesis of...

Embodiment 2

[0052] Synthesis of compound (3):

[0053]

[0054] In a 1000mL four-neck flask, add compound (2) 5-methylnicotinic acid (100.0g, 0.73mol) and 500mL methanol, and under nitrogen protection, add thionyl chloride (80mL, 1.1mol) dropwise, and keep the temperature at 20-25°C. After the dropwise addition, heat to reflux for 4 hours, TLC shows that the reaction is not complete, add 30 mL of thionyl chloride, continue to heat and reflux for 4 hours, and the reaction is complete. Evaporate under reduced pressure to remove methanol, add 200 mL of ice water, neutralize to weak alkalinity with saturated sodium carbonate solution, extract with ethyl acetate, wash the organic phase with saturated brine, dry over anhydrous sodium sulfate, and remove the solvent by evaporation under reduced pressure to obtain White solid (104.6g, 94.8%).

[0055] Synthesis of compound (4):

[0056]

[0057] In a 100mL three-necked flask, add the product (3) 5-methylnicotinic acid methyl ester (5.0g,...

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Abstract

The invention relates to a method for preparing 5-methyl-3-bromomethylpyridine hydrobromide. The method comprises a step of preparing methyl 5-methyl nicotinate; a step of preparing 5-methyl-3-pyridinemethanol; a step of preparing 5-methyl-3-pyridinemethanol hydrobromide; and a step of preparing 5-methyl-3-bromomethylpyridine hydrobromide. In the step of preparing methyl 5-methyl nicotinate, esterification of 5-methyl nicotinic acid and thionyl chloride is carried out under heating reflux to obtain methyl 5-methyl nicotinate; in the step of preparing 5-methyl-3-pyridinemethanol, a reduction reaction of methyl 5-methyl nicotinate and sodium borohydride is carried out in an organic solvent to obtain 5-methyl-3-pyridinemethanol; in the step of preparing 5-methyl-3-pyridinemethanol hydrobromide, 5-methyl-3-pyridinemethanol reacts with hydrobromic acid to obtain 5-methyl-3-pyridinemethanol hydrobromide; and in the step of preparing 5-methyl-3-bromomethylpyridine hydrobromide, 5-methyl-3-pyridinemethanol hydrobromide reacts with hydrobromic acid in an organic solvent and water is removed from the reaction system to obtain 5-methyl-3-bromomethylpyridine hydrobromide. According to the method, 5-methyl-3-bromomethylpyridine hydrobromide is obtained by four steps; the process is simple; and yield is high.

Description

technical field [0001] The invention belongs to the field of chemical industry, in particular to a pharmaceutical intermediate 5-methyl-3-bromomethylpyridine hydrobromide, specifically a method for preparing 5-methyl-3-bromomethylpyridine hydrobromide salt method. Background technique [0002] 5-Methyl-3-bromomethylpyridine is a key drug intermediate in the development of new drugs. Rupatadine is a new type of drug that interacts with specific receptors and is a potent antagonist of platelet activating factor (PAF) and histamine (H1). Both ES2042421 and WO2006114676 report the method of synthesizing rupatadine by using desloratadine and 5-methyl-3-bromomethylpyridine. WO2013000406 reported the synthesis of a series of anti-allergic benzocycloheptathiophene derivatives, including benzocycloheptathiophene derivatives with 5-methyl-3-bromomethylpyridine as a substituent. Allergy is a worldwide disease, so it is urgent to develop anti-allergic agents with improved efficacy an...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D213/26
CPCC07D213/26
Inventor 鲁彦王进郭建宇黄敏飞熊蕾
Owner SHANGHAI INST OF TECH