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Preparation and detection method of abiraterone Acetate dimer compound

A technology of abiraterone acetate and a detection method, which is applied in the field of preparation and detection of abiraterone acetate dimer compounds, can solve complex preparation methods, low purity and yield of abiraterone acetate dimer compounds, and environmental pollution and other problems, to achieve the effect of simple preparation method

Active Publication Date: 2012-12-12
武汉长联来福制药股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] (1) The preparation method is complicated, and the purity and yield of the obtained abiraterone acetate dimer compound are very low, the purity is only 6.8%, and the yield is only 21.8%
[0012] (2) The use of ether in the preparation process has potential safety hazards and is likely to cause environmental pollution

Method used

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  • Preparation and detection method of abiraterone Acetate dimer compound
  • Preparation and detection method of abiraterone Acetate dimer compound
  • Preparation and detection method of abiraterone Acetate dimer compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Step 101, Synthesis of Compound III

[0047] Under nitrogen protection, 3.98 g of 10 mmol of compound I: 3β-hydroxy-17-iodo-androst-5,16-diene and 3.49 g of 10 mmol of compound II: 17-(3-pyridyl) androst-5,16 -diene-3β-alcohol is placed in the reactor, after adding 100ml of dioxane to dissolve, add 0.69 grams of Pd (PPh 3 ) 4 , 3.18 grams of 30mmol sodium carbonate, refluxed for 26h, reacted completely, cooled to room temperature, filtered, concentrated filtrate, added 30ml of water, extracted with ethyl acetate, concentrated filtrate, obtained 5.58 grams of 9mmol compound III: 3β-hydroxyl-16-(3β -Hydroxyandrost-5,16-dien-17-yl)-17-(3-pyridyl)androst-5,16-diene as crude white solid, yield 90.0%.

[0048] Step 102, synthesis of abiraterone acetate dimer compound

[0049] 5.58 grams of 9 mmol compound III obtained in step 101: 3β-hydroxyl-16-(3β-hydroxyandrosta-5,16-dien-17-yl)-17-(3-pyridyl)androsta-5, Put the crude product of 16-diene in the reactor, add 15ml of pyr...

Embodiment 2

[0054] Step 201, Synthesis of Compound III

[0055] Under nitrogen protection, 7.96 g of 20 mmol of compound I: 3β-hydroxy-17-iodo-androst-5,16-diene and 3.49 g of 10 mmol of compound II: 17-(3-pyridyl) androst-5,16 - Diene-3β-alcohol is placed in the reactor, add 100ml THF to dissolve, then add 0.5g Pd(OAc) into the reactor 2 , 4.14 grams of 30mmol potassium carbonate, refluxed for 26h, the reaction was complete, cooled to room temperature, filtered, concentrated the filtrate, added 30ml of water, extracted with dichloromethane, concentrated the filtrate to obtain 5.2 grams of compound III: 3β-hydroxyl-16-(3β- Hydroxyandrost-5,16-dien-17-yl)-17-(3-pyridyl)androst-5,16-diene as crude white solid, yield 83.9%.

[0056] Step 202, synthesizing abiraterone acetate dimer compound

[0057] 5.2 grams of 8.4 mmol of compound III obtained in step 201: 3β-hydroxyl-16-(3β-hydroxyandrost-5,16-dien-17-yl)-17-(3-pyridyl)androsta- Put the crude product of 5,16-diene in a reactor, add 15ml...

Embodiment 3

[0062] Step 301, Synthesis of Compound III

[0063] Under nitrogen protection, 11.94 g of 30 mmol of compound I: 3β-hydroxy-17-iodo-androst-5,16-diene and 3.49 g of 10 mmol of compound II: 17-(3-pyridyl) androst-5,16 -diene-3β-alcohol is placed in the reactor, after adding 100ml of acetonitrile to dissolve, add 0.8 g of PdCl to the reactor 2 (MeCN) 2, 6.5 grams of 20mmol cesium carbonate, refluxed for 20h, the reaction was complete, cooled to room temperature, filtered, the filtrate was concentrated, 30ml of water was added, extracted with chloroform, and the filtrate was concentrated to obtain 5.3 grams of compound III: 3β-hydroxyl-16-(3β- Hydroxyandrost-5,16-dien-17-yl)-17-(3-pyridyl)androst-5,16-diene as crude white solid, yield 85.5%.

[0064] Step 302, Synthesizing Abiraterone Acetate Dimer Compound

[0065] 5.3 grams of 8.6 mmol of compound III obtained in step 301: 3β-hydroxyl-16-(3β-hydroxyandrost-5,16-diene-17-yl)-17-(3-pyridyl)androsta- Put the crude product of 5...

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Abstract

The invention discloses a preparation and detection method of an abiraterone acetate dimer compound, and relates to the of field pharmacy. The dimer compound is 3 beta-acetyl-16-(3 beta-acetyl androstane-5,16-diene-17-base)-17-(3-pyridyl) androsterone-5,16-diene. The method is as follows: adding compounds I and II into a reactor; dissolving the compounds and adding a palladium catalyst and alkali into the reactor; cooling to room temperature; filtering; concentrating; adding water; extracting; concentrating to obtain a compound III crude product; placing the crude product in the reactor; adding pyridine and an acetyl compound; stirring at room temperature till complete reaction; concentrating to remove pyridine and the acetyl compound; adding water, extracting and concentrating to obtain a dimer compound crude; and dissolving the dimer compound crude, washing, drying, filtering, concentrating and recrystallizing to obtain the abiraterone acetate dimer compound. According to high performance liquid chromatography detection and calculation by an area normalization method, the prepared dimer compound has a purity up to 98% and a yield higher than 80%.

Description

technical field [0001] The invention relates to the field of pharmacy, in particular to a method for preparing and detecting an abiraterone acetate dimer compound. Background technique [0002] Abiraterone acetate (Abiraterone acetate) is an oral drug CYP17 inhibitor combined with prednisone, jointly developed by Cancer Research UK and BTG, by inhibiting the cleavage of steroid (class) 17α-hydroxylase / C17-20 Enzyme (P450c17) to block testosterone production in patients with refractory prostate cancer and other testosterone-related diseases who have previously received docetaxel-containing chemotherapy. [0003] "Organic Preparations and Procedures International" (1997, volume 29, phase 1, pages 123-134) discloses a synthetic route of abiraterone acetate impurity, which uses (3β)-3-hydroxyl-5-ene-17-sterone Ketone is used as a raw material, and through 4 steps of reduction, substitution, substitution, and acylation, the reaction synthesizes abiraterone acetate, and its chemi...

Claims

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Application Information

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IPC IPC(8): C07J43/00G01N30/02
Inventor 苏江涛刘伟国杨珍知
Owner 武汉长联来福制药股份有限公司
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