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Preparation of rupatadine or salt thereof

The technology of a compound and acyloxy base is applied in the field of preparation of rupatadine or its salt, which can solve the problems of harsh operating conditions, long reaction time, expensive reagent sodium dihydroaluminate, etc., and achieve low production cost and high reaction rate. The effect of short time and cheap reagents

Inactive Publication Date: 2009-08-05
FOSHAN DAYI TECH LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the operating conditions of this method are harsh, and POCl 3 Strong corrosiveness, especially the distillation process requires high equipment
[0011] In U.S. Patent No. 5,407,941, a method for reducing lithium aluminum hydride as a reducing agent in tetrahydrofuran solution is disclosed, but when lithium aluminum hydride is used as a reducing agent for reduction, the requirements for operating conditions are relatively high, and the reagent lithium aluminum hydride more expensive
[0012] In Chinese patent application 200510070952.1, a method for preparing rupatadine by reducing amide with sodium dihydroaluminate (Red-Al) is disclosed. This method has the disadvantages of long reaction time and expensive reagent sodium dihydroaluminate

Method used

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  • Preparation of rupatadine or salt thereof
  • Preparation of rupatadine or salt thereof
  • Preparation of rupatadine or salt thereof

Examples

Experimental program
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Embodiment 1

[0032] Add 3.78g (0.1 mole) of sodium borohydride to a 100ml single-necked round bottom flask, then add 50ml of tetrahydrofuran, place it on an ice bath, and stir it electromagnetically. Another 11.40 g of trifluoroacetic acid was dissolved in 10 ml of tetrahydrofuran to form a solution, and the solution was dropped into the above-mentioned flask within 30 minutes to prepare sodium trifluoroacetoxyborohydride. Get another 250ml single-necked round bottom flask, add 4.30g (0.01 moles) of the compound of formula I, add 10ml tetrahydrofuran again, electromagnetic stirring, the sodium trifluoroacetoxyborohydride that above-mentioned generation is added dropwise, then material temperature is raised to 30°C, keep for 2 hours. Cool the material to 0°C with an ice bath, slowly drop into 50ml of 10% hydrochloric acid solution, measure the pH to 1, then evaporate most of the tetrahydrofuran on a rotary evaporator, and precipitate a solid, then add 100ml of water, heat to reflux, and kee...

Embodiment 2

[0035]Add 4.30 g (0.01 mol) of the compound of formula I, 3.78 g (0.1 mol) of sodium borohydride, and 50 ml of tetrahydrofuran into a 250 ml single-necked round bottom flask, place it on an ice bath, and stir it electromagnetically. Another 11.40 g of trifluoroacetic acid was dissolved in 10 ml of tetrahydrofuran to form a solution. The solution was dropped into the above-mentioned flask within 30 minutes, and then the temperature of the material was raised to 30° C. and kept for 2 hours. Cool the material to 0°C with an ice bath, slowly drop into 50ml of 10% hydrochloric acid solution, measure the pH to 1, then evaporate most of the tetrahydrofuran on a rotary evaporator, and precipitate a solid, then add 100ml of water, heat to reflux, and keep For 10 minutes, dissolve the precipitated solid, cool to 0°C, add 6 mol / L sodium hydroxide solution until the pH value reaches about 8, extract with ethyl acetate, then dry with a desiccant, evaporate the solvent to obtain Lu Patadine...

Embodiment 3

[0037] Carry out in the same manner as in Example 2, the difference is that the acyloxy alkali metal borohydride is potassium trifluoroacetoxy borohydride, the aprotic solvent is diethyl ether, and the reaction temperature is the heating reflux temperature of diethyl ether, heating The reflux time was 1.5 hours, and 3.01 g of rupatadine product was obtained with a yield of 72.36%. HPLC purity 97.9%. The melting point is 58-60 degrees.

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Abstract

The invention relates to a method for preparing rupatadine and salt thereof, which comprises the following steps: directly adding acyloxy alkali metal borohydride or generating the acyloxy alkali metal borohydride through an in-situ reaction; and performing a reduction reaction of the acyloxy alkali metal borohydride and a compound shown in a formula (I) to prepare the rupatadine. The method has the advantages of simple and convenient operation, short reaction time, cheap adopted reagents, and lower production cost.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a preparation method of rupatadine or a salt thereof. Background technique [0002] Rupatadine and its salts have dual effects of antihistamine and antagonizing platelet activating factor (PAF). The drug was launched in Europe in 2003 and is used in the treatment of allergic rhinitis and hay fever, and has broad market prospects. The chemical structural formula of rupatadine is as follows: [0003] [0004] The preparation method of rupatadine mainly contains two kinds, and one is to use decarboxylated loratadine and 3,5-lutidine as raw materials, and first 3,5-lutidine is subjected to bromination to generate 3- Methyl-5-bromomethylpyridine is then reacted with decarboxylated loratadine to prepare rupatadine. The synthetic route is as follows: [0005] [0006] The second is to use decarboxylated loratadine as a raw material to condense with 5-methylnicotinic acid to form an amid...

Claims

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Application Information

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IPC IPC(8): C07D401/14
CPCC07D401/14A61P7/02A61P11/02
Inventor 唐良伟雍智全谭培雷安胜胡文慧韩为跃闻亚磊
Owner FOSHAN DAYI TECH LTD
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