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

A kind of preparation method of letrozole

A technology of letrozole and triazole, which is applied in the field of drug synthesis, can solve the problems of unsuitability for industrialization, poor reactivity, and high risk, and achieve the effect of low price, low cost, and few by-products

Active Publication Date: 2022-03-11
南京亿华药业有限公司
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The first step of this route has poor reactivity between halogenated hydrocarbons and esters, and requires the use of super-strong base n-butyllithium, which is dangerous and harsh, and is not suitable for industrialization. The reaction process is as follows:

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
  • A kind of preparation method of letrozole
  • A kind of preparation method of letrozole
  • A kind of preparation method of letrozole

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] (1) Synthesis of 4- (1- (1H-1, 2,4-triazole) hydroxymethyl) benzene (Compound 3)

[0049] In the 500ml three-glass round bottom flask, the cyanobenzoate (compound 1, 12.92 mol), triazole (Compound 2, 66.4 g, 0.96 mol) and tetrahydrofuran were added, and stirred was opened, heated to 40 ° C. The reaction was 12 hours, the reaction was stopped, and the solvent was evaporated under reduced pressure. MS [m + 1] + = 201.09.

[0050] (2) 4- (1- (1H-1, 2,4-triazole) chloromethyl) benzene (Compound 4) synthesis

[0051]The results obtained above were added to the 2L three flask, and a sulfoxide (1776 g, 13.2 mol) was added, and the reflux reaction was heated to about 80 ° C for 6 hours. After the reaction, normal pressure was evaporated. Excessive chlorinated sulfoxide, the resulting product was rinsed three times with water, and after the rins were completed, the filter cake was transferred to the flask, and about 500 ml of dichloromethane was added, and the organic layer was wash...

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 discloses a preparation method of letrozole, which comprises the following steps: adding p-cyanobenzaldehyde and triazole into a solvent, and obtaining 4-(1-(1H-1,2,4-triazole Azole) hydroxymethyl) benzonitrile; Thionyl chloride is added to the above product; The above product and tert-butanol are added to the solvent, and the catalyst is added to react to obtain 4-(1-(1H-1,2, 4-triazole) chloromethyl) benzoyl tert-butylamine; this product is added to solvent, Grignard reagent, reacts to obtain 4,4'-((1H-1,2,4-triazole-1-yl ) methyl) bis (N ‑ (tert-butyl) benzamide); phosphorus oxychloride is added, and letrozole is obtained after reaction. The reaction routes of the present invention are relatively mild, do not involve reactions under harsh conditions, do not involve high-risk processes, and are suitable for industrialization.

Description

Technical field [0001] The present invention relates to a method of ulzazole, belonging to the field of drug synthesis. Background technique [0002] Cozole, chemical name 1- [Double (4-cyanophenyl) methyl] -1,2,4-triazole; 4, 4 '- (1 H-1, 2, 4-triazole) 1-yormyl) - bisphenyl nitrile is a new type, highly-specific benzole chemical derivative, which belongs to the third generation aromase inhibitor. Crazazole is carried out by inhibiting aromatase to reduce estrogen levels, thereby eliminating the stimulation of estrogen on tumor growth and used for endocrine treatment of breast cancer. [0003] To the inner activity of the bezipole than the first generation of aromatase inhibitors, 1,500 times, due to its high selectivity, it does not affect glucocorticoids, salt corticoids and thyroid function, and large doses of adrenal cortex There is no inhibitory effect, and therefore has a higher therapeutic index. The pre-clinical studies have shown that there is no potential toxicity, no ...

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): C07D249/08
CPCC07D249/08
Inventor 杨鹏辉袁和亮张霞
Owner 南京亿华药业有限公司