Method for preparing butyrate clevidipine

A technology of clevidipine butyrate and formic acid, which is applied in the direction of organic chemistry, can solve the problems of many impurities, not suitable for mass production of products, and difficult control of synthesis reactions, etc., and achieve the effect of simple process and low cost

Inactive Publication Date: 2010-06-30
SUN YAT SEN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
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Benefits of technology

This new technology allows for better control over how much chemicals are added during reactions between different substances like an ester compound called 3-(pivaloledimensional)-(2',3'-dihydroxypropyltrimonium). By controlling this addition time, it becomes possible to produce high yields of pure products containing these molecules while also reducing costs associated therewith.

Problems solved by technology

This patented technical problem addressed in this patent relates to improving the efficiency and effectiveness of producing phosphorylated compounds such as caffeidi pimelii nicotinamide mononucleotides due to their ability to effectively reduce blood pressures without causing side effects like excessive bleeding during administration.

Method used

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  • Method for preparing butyrate clevidipine
  • Method for preparing butyrate clevidipine
  • Method for preparing butyrate clevidipine

Examples

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Embodiment 1

[0026] Embodiment 1: (±)-4-(2', 3'-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-5-carboxylic acid methyl-3-formic acid ( II)

[0027] In a round bottom flask, add 2,3-dichlorobenzaldehyde (175g, 1mol), propionitrile acetoacetate (160g, 1.03mol) and 3-amino-2-butenoic acid methyl ester (115g, 1mol), iso Propanol was used as a solvent, and the reaction was carried out at 50°C for 12 hours. After removing the solvent under reduced pressure, cool to room temperature, add ethanol / water mixed solution of sodium hydroxide, stir for 5 h, then add 1 L of water, and wash the aqueous phase with dichloromethane. 300 mL of phosphoric acid was slowly added to the water phase, and a yellow precipitate was formed, and 273.2 g of solid was obtained by suction filtration, with a yield of 77%. IR (KBr, cm -1 ): 3344, 2950, ​​1656, 1477, 1229, 779. 1 H NMR (DMSO, ppm): δ=11.59(s, 1H), 8.81(s, 1H), 7.38-7.21(m, 3H), 5.30(s, 1H), 3.48(s, 3H), 2.23(s , 3H), 2.22(s, 3H); 13 C NMR (DMSO, ppm...

Embodiment 2

[0028] Example 2: (±)-4-(2', 3'-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid methyl (butyl Acyloxymethyl) ester (III)

[0029] Add (±)-4-(2',3'-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-5-carboxylic acid methyl-3- Formic acid (171.0g, 0.48mol), anhydrous sodium carbonate (101.8g, 0.96mol) and 3L of DMF were added, and chloromethyl n-butyrate (61.8mL, 0.49mol) was added, and the reaction was stirred at 60°C for 12h. The reaction liquid was cooled to room temperature, 2L of ethyl acetate and 1L of water were added, the organic phase was separated, and the solvent was removed after drying to obtain a yellow solid. Repeated recrystallization with ethyl acetate / petroleum ether gave 97.5 g of white (slightly bright yellow) solid, with a yield of about 45%. Mp.136.4°C-138.9°C. Optical rotation: [ a ] D 20 = 0 (c=5, MeOH). The purity by HPL...

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Abstract

The invention discloses a method for preparing butyrate clevidipine. The method comprises that 2, 3-dichlorobenzaldehyde, acetoacetate propionitrile ester and 3-amino-2-methyl crotonate are mixed and one-pot Hantzsch reaction is conducted, base catalyst is added to remove 2-cyanoethyl to obtain key intermediate, the key intermediate reacts with n-butyric acid chloromethyl ester to obtain butyrate clevidipine crude product, and the crude product is recrystallized to obtain high-purity butyrate clevidipine. Raw material 3-amino-2-methyl crotonate can be prepared by using low-price methyl acetoacetate. Raw material acetoacetate propionitrile ester can be prepared by using diketene. The synthesis of all raw materials requires no chromatographic separation for purification. The intermediate is synthesized through one-pot Hantzsch reaction, the reaction speed is fast, the condition is mild, the technological reliability is high and the purity of the intermediate is high. The conditions for the reaction of the key intermediate and the n-butyric acid chloromethyl ester can be easily controlled, the operation is simple and convenient, the cost is low, the post treatment requires no chromatographic separation for purification, the purity of the obtained butyrate clevidipine is above 99.5 percent and the mass production can be realized.

Description

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Claims

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Application Information

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Owner SUN YAT SEN UNIV
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