Preparation method of dutasteride intermediate

A technology of crystals and compounds, applied in the field of drug synthesis, can solve the problems of unsuitability for industrial production, complicated operation, etc., and achieve the effects of cost reduction, simplified operation and high purity

Inactive Publication Date: 2013-04-24
SHANGHAI INST OF PHARMA IND +1
View PDF5 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] The method has simple reaction conditions, low cost, and does not use expensive catalysts, but requires multiple acetone recrystallizations to remove the by-product 5-β isomers brought about by the reaction, which makes the operation cumbersome and unsuitable for industrial production

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 dutasteride intermediate
  • Preparation method of dutasteride intermediate
  • Preparation method of dutasteride intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 13

[0038] Preparation of Example 13-Carbonyl-4-aza-5α-androst-17β-carboxylic acid crude product

[0039]

[0040] Formula I Formula II

[0041] In a 5L reaction flask equipped with a reflux condenser, 3-carbonyl-4-aza-5-androstene-17β-carboxylic acid (compound of formula II) (66.0g, 208mmol) and K 2 CO 3 (430.0g, 3.12mol) was added into DMF (2500ml), stirred, and heated to 140°C. Then slowly drop formic acid (1716ml) in the above-mentioned solution, drip in about 2 hours, continue to react for 4-6 hours, until TLC detects that the raw material point disappears. Then concentrated under reduced pressure to about 2100ml, cooled to room temperature, added 2100ml of water, stirred overnight in an ice-water bath, washed with water, and dried to obtain 53.2g of light yellow solid. ESI: 320.2[M+H] + . As detected by HPLC, the 5-beta isomer was 24.7%.

Embodiment 2

[0043] Preparation of crude 3-carbonyl-4-aza-5α-androst-17β-carboxylic acid

[0044]

[0045] In a 5L reaction flask equipped with a reflux condenser, 3-carbonyl-4-aza-5-androstene-17β-carboxylic acid (66.0g, 208mmol) and K 2 CO 3 (430.0g, 3.12mol) was added into DMF (2500ml), stirred, and heated to 150°C. Then, in the above-mentioned solution, formic acid (1452ml) was slowly added dropwise for about 1.7 hours, and the reaction was continued for 4-6 hours until the TLC detection raw material point disappeared. Then concentrated under reduced pressure to about 1950ml, cooled to room temperature, added 1950ml of water, stirred overnight in an ice-water bath, washed with water, and dried to obtain 52.8g of light yellow solid. ESI: 320.2[M+H] + . As detected by HPLC, the 5-beta isomer was 24.8%.

Embodiment 33

[0046] Example 33- Preparation of the crude product of carbonyl-4-aza-5α-androst-17β-carboxylic acid

[0047]

[0048] In a 5L reaction flask equipped with a reflux condenser, 3-carbonyl-4-aza-5-androstene-17β-carboxylic acid (66.0g, 208mmol) and K 2 CO 3 (430.0g, 3.12mol) was added into DMF (2500ml), stirred, and heated to 145°C. Then, in the above-mentioned solution, formic acid (1848ml) was slowly added dropwise for about 2.2 hours, and the reaction was continued for 4-6 hours until the TLC detection raw material point disappeared. Then concentrated under reduced pressure to about 2200ml, cooled to room temperature, added 2200ml of water, stirred overnight in an ice-water bath, washed with water, and dried to obtain 53.0g of light yellow solid. ESI: 320.2[M+H] + . As detected by HPLC, the 5-beta isomer was 24.5%.

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 relates to a preparation method of dutasteride intermediate, and specifically relates to a preparation method of 3-carbonyl-4-aza-5[alpha]-androstane-17[beta]-carboxylic acid. According to the preparation method, for hydrogenation, a carboxylic acid derivative is used as a hydrogen donor to perform transfer hydrogenation, so that hydrogen pressure reduction is prevented and expensive catalysts such as PtO2, Pd / C, raneys nickel, zinc powder and the like are not needed; and for purification, a specific alcoholic solvent is used to perform crystallization, so that 5-beta isomer produced by reduction can be separated effectively. The obtained product has high purity, operations are simplified and the method is suitable for industrialized production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a preparation method of dutasteride intermediate 3-carbonyl-4-aza-5α-androst-17β-carboxylic acid. Background technique [0002] Dutasteride is a second-generation 5α-reductase inhibitor, a drug that simultaneously inhibits type I and type II 5α-reductase, developed by Glaxo and launched in the United States on October 10, 2002 Listed, for the treatment of benign prostatic hyperplasia (BHP), has the following structural formula. [0003] dutasteride [0004] Regarding the preparation method of dutasteride, there are many published patents. Such as the preparation method described in CN1131424A, CN1668632A and CN101759762A. In addition, some domestic and foreign documents have also reported the preparation method of dutasteride, such as the 1759-1761 page 1759-1761 of the 20th phase of the 15th volume of the Chinese Journal of New Drugs in 2006, which reported the 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 Applications(China)
IPC IPC(8): C07J73/00
Inventor 杨玉雷袁哲东唐兆成
Owner SHANGHAI INST OF PHARMA IND
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
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap