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Preparation method of urapidil by reverse phase transfer catalysis

A catalytic preparation, urapidil technology, applied in the direction of chemical instruments and methods, physical/chemical process catalysts, organic compounds/hydrides/coordination complex catalysts, etc., can solve the problem of not providing product purity and difficult to achieve pharmaceutical purity and other problems, to achieve the effects of easy control of reaction conditions, shortened reaction time, and simple operation

Inactive Publication Date: 2011-12-28
ZHENGZHOU UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0015] (2) This method does not provide the purity of the product. When we repeated the reaction, we found that during the precipitation of the crude urapidil, the unreacted raw materials were accompanied by the precipitation of the product, making the product purity 85-90%. After crystallization, the purity is difficult to reach more than 98.5% of medicinal purity, therefore, the purity problem of the product needs to be solved

Method used

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  • Preparation method of urapidil by reverse phase transfer catalysis
  • Preparation method of urapidil by reverse phase transfer catalysis
  • Preparation method of urapidil by reverse phase transfer catalysis

Examples

Experimental program
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Effect test

Embodiment 1

[0031] 1-(2-Methoxyphenyl)piperazine hydrochloride (5.67g, 0.025mol) was added to Na 2 CO 3 (5.27g, 0.050mol) and the mixture of 25ml water, be heated to 90 ℃, add 6-(3-chloropropyl)-1,3-dimethyluracil (5.00g, 0.022mol) in batches, Then add 0.2 g of β-cyclodextrin, complete the addition, react for 6 hours, add water, stir and cool, a white substance precipitates, filter under reduced pressure, and dry at room temperature to obtain 6.91 g of white powdery solid, with a yield of 82.6% and a purity of 99.91%. . m.p.136~138°C. 1 HNMR (CDCl 3 , 400 MHz) δ: 1.89-1.93(m, 2H, CH 2 ), 2.67-2.69 (m, 2H, CH 2 N), 2.77-2.78 (m, 4H, CH 2 N), 3.10-3.11(m, 4H, CH 2 N), 3.18-3.20 (m, 2H, CH 2 N), 3.33(s, 4H, CH 3 N), 3.42(s, 3H, CH 3 N), 3.89(s, 3H, CH 3 O), 4.80(s, H, CH=), 6.89-6.98(m, 3H, ArH), 7.04-7.08(m, H, ArH).

[0032] attached figure 1 The HPLC figure analysis result of urapidil standard substance is as follows:

[0033]

experiment example 1

[0034] The HPLC figure analysis result of experimental example 1 gained urapidil is as follows:

[0035]

Embodiment 2

[0037] 1-(2-methoxyphenyl)piperazine hydrochloride (12.84g, 0.056mol) was added into K 2 CO 3 (11.9g, 0.086mol) and the mixture of 50ml water, be heated to 96 ℃, add 6-(3-chloropropyl)-1,3-dimethyluracil (10g, 0.043mol) in batches, then Add 0.4 g of cetyltrimethylammonium bromide, after the addition is complete, react for 4 hours, add water, stir and cool, a white substance precipitates, filter under reduced pressure, and dry at room temperature to obtain 13.82 g of a white powdery solid, yield 83.0% , with a purity of 99.83%. Melting point and spectral data are the same as above.

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Abstract

The invention discloses a preparation method for urapidil, and relates to an inverse phase transfer catalysis method for preparing urapidil, and belongs to the technical field of organic synthesis. The method comprises the following steps that: water is adopted as a solvent; an inorganic alkaline substance is adopted as an acid binding agent; 6-(3-chloropropyl)-1,3-dimethyluracil (I) reacts with 1-(2-methoxyphenyl)piperazine hydrochloride (II) in the presence of an inverse phase transfer catalyst to generate 6-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]-propyl]-amino]-1,3-dimethyl-uracil (III, urapidil). With the method, the high-selectivity and high-yield preparation of the urapidil can be realized; the prepared urapidil has high purity, wherein the purity of the urapidil is more than 99.5%;the conversion rate is high; the yield can reach 80%; the reaction conditions are mild; the selectivity is good; the post-treatment is simple; the method is environmental-friendly, and is suitable for the industrial production.

Description

technical field [0001] The invention relates to a preparation method of uradil, in particular to the preparation of uradil by a reverse phase transfer catalysis method, which belongs to the technical field of organic synthesis. Background technique [0002] Urapidil is a uracil substituted by benzoxinazole, its chemical name is 6-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]-propyl]-amino] -1, 3-Dimethyl-2, 4(1H, 3H)-pyrimidinedione, the English name is 6-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]amino]-1 ,3-dimethyl-uracil, the structural formula is: [0003] [0004] The trade names of urapidil hydrochloride are ladenidine, Ebrantil, and lixidine. Its mechanism of action is 1 Receptor blockers and weaker beta blockers have both peripheral and central effects. By blocking peripheral postsynaptic alpha 1 Dilate blood vessels after the receptor, and directly excite the central 5-HT 1A The receptor reduces the sympathetic feedback modulation of the medullary cardiovascu...

Claims

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Application Information

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IPC IPC(8): C07D239/545B01J31/06B01J31/02
Inventor 李雯朱松林马晓青陈水库朱成功杜孟洪余卫晓姬力莎袁坤黄占海
Owner ZHENGZHOU UNIV
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