- New and efficient technique for the synthesis of Urapidil using β-cyclodextrin as an inverse phase-transfer catalyst
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A novel and efficient procedure has been developed for the preparation of Urapidil, (6-({3-4-(2-methoxyphenyl) piperazin-1-yl] propyl} amino)-1,3-dimethyl pyrimidine-2,4-(1H, 3H)-dione), from 6-[(3-chloropropyl) amino]-1, 3-dimethyluracil and 1-(2-methoxyphenyl) piperazine hydrochloride under inverse phase-transfer catalysis (IPTC) conditions. To optimize the reaction conditions, the alkylation reaction was carried out with a range of inverse phase-transfer catalysts, agitation speeds, reaction times, reaction temperatures, mole ratios and catalyst loadings. In addition, the factors affecting the rate of reaction were studied and the rate constant obtained is consistent with the pseudo-first order rate equation. When β-cyclodextrin was used as a catalyst, Urapidil was obtained as a white crystalline powder in 82.6% isolated yield with 99.6% purity after 2-3 h reaction in alkaline aqueous media at 95°C with an agitation rate of 1500 rpm.
- Li, Wen,Zhang, Wenya,Ma, Xiaoqing,Wang, Panpan,Du, Menghong
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- Preparation method of urapidil
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The invention provides a preparation method of urapidil. The preparation method comprises the following steps: mixing 1, 3-dimethyl-6-aminouracil with 3-amino-1-propanol, and carrying out a reaction so as to prepare 6-(3-hydroxypropylamino)-1, 3-dimethyluracil; mixing 6-(3-hydroxypropylamino)-1, 3-dimethyluracil and thionyl chloride to react so as to prepare 6-(3-chloropropylamino)-1, 3-dimethyluracil; and enabling 6-(3-chloropropyl amino)-1, 3-dimethyluracil to react with 1-(2-methoxyphenyl) piperazine hydrochloride so as to obtain the urapidil. The preparation method has the advantages of simple operation, cheap and easily available reagents, few side reactions, high yield, good purity of the obtained product, and facilitation of industrial production.
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- New method for preparing urapidil
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The invention relates to a new preparation method of urapidil hydrochloride. The method takes 3-[4-(2-methoxyphenyl)piperazine-1-yl]propylamine and 6-chloro-1,3-dimethyluracil as intermediates to prepare urapidil, and then urapidil hydrochloride is obtained by salifying. The new preparation technology of urapidil hydrochloride is characterized in that the raw material structure is simple, water isadopted as a solvent, post-treatment is easy, the product purity is high, the total weight of related substances is less than 0.3%, the yield is high, the total yield is higher than 79%, and the preparation technology is suitable for industrialized production.
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Paragraph 0032-0034; 0037-0039; 0042-0045; 0048-0051; 0054
(2019/04/15)
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- Urapidil a preparation process of a hydrochloric acid
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The invention relates to a new preparation technique of urapidil hydrochloride, belonging to the technical field of drug synthesis. According to the new preparation technique, a Pd/NHC catalytic system is directly utilized to catalyze 6-(3-chloropropyl)-1,3-dimethyluracil and 1-(2-methoxyphenyl)piperazino hydrochloride to prepare urapidil, and the urapidil is further acidified to prepare the urapidil hydrochloride. The new preparation technique of urapidil hydrochloride has the advantages of simple structure of raw materials, no need of abundant phase-transfer catalysts, fewer side reactions, easy after-treatment, favorable product selectivity and higher yield, and is suitable for industrial production; and the related substance content is less than 0.0047%, and the total yield is greater than 58%.
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Paragraph 0037
(2017/02/09)
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- Synthesis and physico chemical properties of the antihypertensive agent urapidil
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6-{3-[4-(o-Methoxyphenyl)-1-piperazinyl]-propylamino}-1,3-dimethyluracil (Urapidil, Ebrantil) is a new antihypertensive agent whose synthesis and physico-chemical properties are described. The size of the permeation constant K(D) of the passive transport through collodion-lecithin membranes and the value of the partition coefficient P in the neutral area indicate a good absorption and uniform distribution of the substance in the organism.
- Klemm,Pruesse,Krueger
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p. 1895 - 1897
(2007/10/05)
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