Finasteride chiral impurity (5beta-finasteride) synthesizing and purifying method

A technology of finasteride and chirality, which is applied in the field of chemical synthesis of steroid medicines, and can solve problems such as unreported synthetic methods

Active Publication Date: 2018-11-06
ZHEJIANG XIANJU PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Through literature search, there is no report on the synthesis method of this impurity

Method used

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  • Finasteride chiral impurity (5beta-finasteride) synthesizing and purifying method
  • Finasteride chiral impurity (5beta-finasteride) synthesizing and purifying method
  • Finasteride chiral impurity (5beta-finasteride) synthesizing and purifying method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] The first step, catalytic hydrogenation: add bisamide (20g, 1W), 5% palladium carbon (10g, 0.5W), p-toluenesulfonic acid (4g, 0.2W) and glacial acetic acid (140g, 7W) in the reaction flask , Nitrogen protection, hydrogen replacement, hydrogen replacement three times, heat preservation at 60 ° C for 8 hours, nitrogen replacement to terminate the hydrogenation reaction. Raise the temperature to 80°C, filter off the palladium carbon while it is hot; concentrate the filtrate to dryness under reduced pressure to obtain a hydride, which is sampled for detection. The main peak content of 5β-chiral hydride in the hydride is 28.8%.

[0044] The second step, refining: add dichloromethane (400ml, 20V) to the hydride, stir to dissolve; sequentially use 10% sodium carbonate solution (180ml, 9V), water (100ml, 5V), water (100ml, 5V) Wash and separate. Collect the dichloromethane layer and concentrate under reduced pressure to a paste, pour into ethyl acetate (200ml, 10V) and concen...

Embodiment 2

[0048] The first step, catalytic hydrogenation: add bisamide (20g, 1W), 5% palladium carbon (10g, 0.5W), p-toluenesulfonic acid (10g, 0.5W) and glacial acetic acid (200g, 10W) ​​in the reaction flask , Nitrogen protection, hydrogen replacement three times through hydrogen insulation 40 ℃ reaction for 12h, nitrogen replacement to terminate the hydrogenation reaction. Raise the temperature to 80°C, filter off the palladium carbon while it is hot; concentrate the filtrate to dryness under reduced pressure to obtain a hydride, which is sampled for detection. The main peak content of 5β-chiral hydride in the hydride is 30.2%.

[0049] The second step, refining: add chloroform (400ml, 20V) to the hydride, stir to dissolve; sequentially use 10% sodium carbonate solution (180ml, 9V), water (100ml, 5V), water (100ml, 5V) Wash and separate. Collect the chloroform layer and concentrate it to a paste under reduced pressure, pour into ethyl formate (200ml, 10V) and concentrate to about (...

Embodiment 3

[0053] The first step, catalytic hydrogenation: add bisamide (20g, 1W), 10% palladium carbon (5g, 0.25W), methanesulfonic acid (1g, 0.05W), glacial acetic acid (100g, 5W) in the reaction flask, Nitrogen protection, hydrogen replacement, hydrogen replacement three times, heat preservation at 80°C for 6 hours, nitrogen replacement to terminate the hydrogenation reaction. The palladium carbon was filtered off while it was hot; the filtrate was concentrated to dryness under reduced pressure to obtain a hydride, which was sampled for detection. The main peak content of 5β-chiral hydride in the hydride is 26.1%.

[0054] The second step, refining: add dichloromethane (400ml, 20V) to the hydride, stir to dissolve; sequentially use 10% sodium carbonate solution (180ml, 9V), water (100ml, 5V), water (100ml, 5V) Wash and separate. Collect the dichloromethane layer and concentrate it to a paste under reduced pressure, pour in isopropyl acetate (200ml, 10V) and concentrate to about (120...

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Abstract

The invention discloses a finasteride chiral impurity (5beta-finasteride) synthesizing and purifying method. A diamide compound (formula 1) is used as a raw material, and a target product of formula 3is obtained through catalytic hydrogenation, refining, dehydrogenating and purifying, wherein a synthetic route is shown in the specification. The 5beta-finasteride is an unavoidable chiral impurityin a production process of finasteride, the separation and purification of the finasteride have important signification to impurity analysis of the finasteride, and provide great convenience to quality research of a finasteride active compound.

Description

technical field [0001] The invention belongs to the field of chemical synthesis of steroid medicines, and in particular relates to a preparation method of finasteride chiral impurity 5β-finasteride. Background technique [0002] Finasteride, chemical name Finasteride, molecular formula C 23 h 36 N 2 O, molecular weight 372.54, CAS registration number 98319-26-7, its structural formula is shown below. [0003] [0004] Finasteride is a 4-azasteroid that is a specific inhibitor of type II 5α-reductase, an intracellular enzyme involved in the metabolism of testosterone to the stronger dihydrotestosterone. Benign prostatic hyperplasia, or enlarged prostate, depends on the conversion of testosterone to dihydrotestosterone in the prostate. This medicine is very effective in reducing dihydrotestosterone in the blood and in the prostate. Finasteride has no affinity for the androgen receptor. Finasteride belongs to the 5α reductase inhibitor, which is through its hormone act...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J73/00
CPCC07J73/005
Inventor 王川戴静方伟明
Owner ZHEJIANG XIANJU PHARMA
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