Unlock instant, AI-driven research and patent intelligence for your innovation.

The synthetic method of anastrozole key intermediate

A technology of anastrozole and intermediates, which is applied in the field of preparation of pharmaceutical intermediates, can solve the problems of high reaction cost, lengthy route, high reaction risk and the like, and achieves the effects of ensuring drug quality, low cost and simple operation.

Active Publication Date: 2020-11-10
HANGZHOU ZHONGMEI HUADONG PHARMA +1
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] It is not difficult to find out from above-mentioned synthetic route, method 1 and 2 route lengthy, and all need to use highly toxic cyanation reagent, reaction risk is big, is not suitable for industrialized production; The cost is high, and the palladium catalyst is easy to remain in the product, which is difficult to remove, until the final product anastrozole contains palladium residue, which cannot meet the drug quality standards

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
  • The synthetic method of anastrozole key intermediate
  • The synthetic method of anastrozole key intermediate
  • The synthetic method of anastrozole key intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Dimethyl sulfoxide (50mL) was added to a three-necked flask, and 3,5-diiodotoluene (II) (6.88g, 0.02mol), 2-methyl-2-cyanopropionic acid (III ) (4.61 g, 0.04 mol), cesium carbonate (4.00 g, 0.4 mol), CuOAc (0.49 g, 0.004 mol) and 1,10-phenanthroline (1.46 g, 0.008 mol). The temperature was raised to 140° C., and the reaction was carried out for 10 hours. Cool down to room temperature, add water slowly to precipitate a solid, dissolve the solid with ethanol (20 mL), cool and recrystallize after activated carbon decolorization, filter and dry to obtain an off-white solid product (3.78 g, yield: 83.4%).

Embodiment 2

[0035] Add N,N-dimethylformamide (50mL) into the three-necked flask, and add 3,5-dibromotoluene (II) (5.0g, 0.02mol) under nitrogen protection, 2-methyl-2-cyano Propionic acid (III) (5.76 g, 0.05 mol), potassium phosphate (17.14 g, 0.08 mol), CuI (0.38 g, 0.002 mol) and 2,2'-bipyridine (0.32 g, 0.002 mol). The temperature was raised to 150° C. and the reaction was refluxed for 12 hours. Cool down to room temperature, add water slowly to precipitate a solid, dissolve the solid with ethanol (20 mL), cool and recrystallize after activated carbon decolorization, filter and dry to obtain an off-white solid product (3.67 g, yield: 81.1%).

Embodiment 3

[0037] Add 1,4-dioxane (50mL) into the three-necked flask, add 3,5-dibromotoluene (II) (5.0g, 0.02mol) under nitrogen protection, 2-methyl-2-cyanopropane Acid (III) (4.61 g, 0.04 mol), sodium ethoxide (4.78 g, 0.07 mol), CuBr (0.43 g, 0.003 mol) and 1,10-phenanthroline (0.73 g, 0.004 mol). The temperature was raised to 110° C. and the reaction was refluxed for 24 hours. Cool down to room temperature, add water slowly to precipitate a solid, dissolve the solid with ethanol (20 mL), cool and recrystallize after activated carbon decolorization, filter and dry to obtain an off-white solid product (3.63 g, yield: 80.2%).

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

PropertyMeasurementUnit
purityaaaaaaaaaa
Login to View More

Abstract

The invention provides a preparation method of an anastrozole key intermediate (I) shown in the description. 3, 5-toluene dihalide (II) and 2-methyl-2-cyanopropionic acid (III) are taken as raw materials and subjected to one-step reaction in the presence of alkali, a solvent and a copper catalyst, and a target product is generated. The method has the advantages of being simple and controllable tooperate, high in product yield, low in cost, environmentally friendly and suitable for large-scale industrial enlarged production.

Description

technical field [0001] The invention belongs to the technical field of preparation of pharmaceutical intermediates, in particular to a method for synthesizing a third-generation aromatase inhibitor anastrozole intermediate. Background technique [0002] Anastrozole (Ananstrozole), chemical name a, a, a', a'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-phenylacetonitrile , is a potent non-steroidal aromatase inhibitor. It can reduce the level of plasma estrogen and inhibit the growth of breast tumors. It is clinically used for the treatment of advanced breast cancer in postmenopausal women, and it is suitable for the condition that cannot be controlled by tamoxifen and other anti-estrogen therapy. Its structural formula is as follows: [0003] [0004] 3,5-bis(2,2'-dimethylcyanomethyl)toluene (I) is an important intermediate of anastrozole, and most of the routes for preparing anastrozole reported at present are 3,5-bis(2 , 2′-Dimethylcyanomethyl) toluene (I) was syn...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07C253/30C07C255/33
CPCC07C253/30C07C255/33
Inventor 郑六军魏文登王慧马波周玉宝
Owner HANGZHOU ZHONGMEI HUADONG PHARMA