Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Preparation method of fibrauretine

A technology of palmetine and intermediates, which is applied in the field of compound preparation, can solve the problems of raw material acquisition restrictions, and achieve the effects of low synthesis cost, simple operation and high purity

Inactive Publication Date: 2011-02-16
太仓浦源医药原料有限公司
View PDF2 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] This method is the same as the second method, and the pollution is more serious, and the acquisition of raw materials is subject to certain restrictions.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of fibrauretine
  • Preparation method of fibrauretine
  • Preparation method of fibrauretine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Synthesis of intermediate one:

[0035] Take a 5L dry three-necked bottle, add 268 grams of 3-bromo-7,8-dimethoxyisoquinoline, 238 grams of 2-(2-hydroxyethyl)-4,5-dimethoxyboronic acid in sequence , 200 grams of anhydrous potassium carbonate and 2.5L of anhydrous dioxane, nitrogen replacement three times under the condition of mechanical stirring, adding 10 grams of Pd (PPh 3 ) 4 , reflux reaction under nitrogen protection conditions, HPLC detection product content no longer rises, stop the reaction, cool to room temperature, and suction filter. The obtained filtrate recovered the solvent under reduced pressure, and the viscous material was dissolved in 2 L of dichloromethane, washed with 2 L of water, dried, and concentrated to obtain 315 g of solid, with a yield of 85.4%, which was directly used for the next reaction without purification.

[0036] Synthesis of Intermediate 2:

[0037] Take a 5L dry three-necked bottle, add 315g of intermediate one and 2L of anhydro...

Embodiment 2

[0041] Synthesis of intermediate one:

[0042] Take a 5L dry three-necked bottle, add 200 grams of 3-bromo-7,8-dimethoxyisoquinoline and 178 grams of 2-(2-hydroxyethyl)-4,5-dimethoxyboronic acid in sequence , 120 grams of anhydrous Na 2 CO 3 and 1.5L of anhydrous toluene, nitrogen replacement three times under the condition of mechanical stirring, adding 15g of Pd(OAc) 2, reflux reaction under the protection of Ar, the HPLC detection product content no longer increased, stop the reaction, cool to 25 ° C, and suction filter. The obtained filtrate recovered the solvent under reduced pressure, the viscous material was dissolved with 1.5 L of dichloromethane, washed with 2 L of water, the obtained organic layer was dried over sodium sulfate, and concentrated to obtain 220 g of solid, with a yield of 80%, which was directly used for the next step reaction without purification.

[0043] Synthesis of Intermediate 2:

[0044] Take a 3L dry three-necked flask, add 220g of intermedi...

Embodiment 3

[0048] Synthesis of intermediate one:

[0049] Take a 3L dry three-necked bottle, add 150g 3-bromo-7,8-dimethoxyisoquinoline, 134g 2-(2-hydroxyethyl)-4,5-dimethoxyboronic acid, 65g Li 2 CO 3 and 1.5L of anhydrous acetone, replaced with nitrogen three times under the condition of mechanical stirring, and added 7g of PdCl 2 , reflux reaction under nitrogen protection conditions, HPLC detection product content no longer rises, stop the reaction, cool to room temperature, and suction filter. The obtained filtrate recovered the solvent under reduced pressure, and the viscous material was dissolved in 1 L of dichloromethane, washed with 1 L of water, dried, and concentrated to obtain 161 g of solid, with a yield of 78%, which was directly used for the next reaction without purification.

[0050] Synthesis of Intermediate 2:

[0051] Take a 2L dry three-necked flask, add 160g of intermediate one and 0.8L of anhydrous acetonitrile, add 120g of triphenylphosphine under nitrogen pro...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a preparation method of fibrauretine, mainly comprising the following steps of: (1) using 3-halo-7,8-dimethoxy isoquinoline of a formula I and 2-(2-hydroxyethyl)-4,5-dimethoxy boric acid of a formula II as raw materials and synthesizing a first intermediate under the actions of a palladium catalyst, alkali and protective gas; (2) further synthesizing the first intermediate into a second intermediate under the actions of Ph3P, CCl4 and acetonitrile; (3) synthesizing the second intermediate into the fibrauretine under the action of an acid-binding agent, wherein in the 3-halo-7,8-dimethoxy isoquinoline of the formula I, X stands for any one of Cl, Br and I. In the invention, the preparation method has a shorter synthetic process line, the used starting materials are synthetic materials and are not limited by natural resources, and the used ancillary materials have lower environment pollution and no amounts of water to discharge; and the invention has the advantages of low synthetic cost and simple operation, and the obtained product has high purity.

Description

technical field [0001] The invention relates to a preparation method of a compound, in particular to a preparation method of palmatine. Background technique [0002] Palmatine, also known as palmatine, chrysanthemum, African tetrandrine, palmitine, palmate tetrandrine, Calystigine, has a broad-spectrum antibacterial effect, and can be used clinically to treat gynecological inflammation, bacillary dysentery, enteritis, respiratory and urinary tract infections, Surgical infection and conjunctivitis, etc. The domestic and foreign market demand for palmatine is hundreds of tons per year. In the past, it was mainly extracted and refined from the dried cane of Caulis Fibraurear, but the current situation is that resources are scarce and supply is in short supply. [0003] At present, the chemical methods for chemically synthesizing palmatine mainly include the following: [0004] Method 1: Chinese patent CN1687064 (disclosure date is October 26, 2005). This method uses 2-methoxy...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D455/03
Inventor 周富荣周伟锋邵林华
Owner 太仓浦源医药原料有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Eureka Blog
Learn More
PatSnap group products