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A kind of synthetic method of abiraterone acetate

A technology of abiraterone acetate and a synthesis method, applied in the directions of steroids, organic chemistry, etc., can solve the problems such as long time of Suzuki coupling reaction, and achieve the advantages of being beneficial to industrialized production, easy to obtain raw materials and high total yield. Effect

Active Publication Date: 2016-04-27
浙江东晖药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage of this route is that the time required for the Suzuki coupling reaction is longer, and the generated product Abiraterone is easy to generate by-products with the raw material alkenyl iodide compound

Method used

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  • A kind of synthetic method of abiraterone acetate
  • A kind of synthetic method of abiraterone acetate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Add 3.3g (10mmol) of dehydroepiandrosterone acetate, 2.5g (12mmol) of aluminum isopropoxide, 10mL of isopropanol, and 10mL of toluene into a 250mL three-neck flask, carry out the reduction reaction at 130°C for 10 hours, cool properly and add molecular sieves 6g (served as desiccant and decolorizer at the same time) heated to reflux for dehydration, cooled and then added 1.6g (11mmol) of 3-bromopyridine, 0.3g (1.1mmol) of palladium acetate, 1.1g (1.1mmol) of triethylamine), and heated to reflux for 15 hours , concentrated, and column chromatography cyclohexane: ethyl acetate (volume ratio) = 5:2 mixed solvent as a developing solvent for separation and purification to obtain 2.34 g of the product with a yield of 60%.

[0023] The melting point is 128~130°C. 1HNMR (400MHz, CDCl3) δ: 1.05(s, 3H, 19-CH3), 1.08(s, 3H, 18-CH3), 2.04(s, 3H, CH3CO2), 3.51~3.58(m, 1H, 3α-H ),5.39(d,J=4.7Hz,1H,6-H),6.00(s,1H,16-H),7.22(dd,J1=4.8Hz,J2=7.8Hz,1H,Py5-H), 7.66 (d, J=7.9Hz, 1H, Py4-H...

Embodiment 2

[0025] Add 3.3g (10mmol) of dehydroepiandrosterone acetate, 2.5g (12mmol) of aluminum isopropoxide, 10mL of isopropanol, and 50mL of toluene into a 250mL three-neck flask, carry out the reduction reaction at 50°C for 15 hours, cool properly and add molecular sieves 1g, 2g of activated carbon (as desiccant and decolorizer at the same time), heating to reflux for dehydration, cooling and then adding 1.6g (11mmol) of 3-bromopyridine, 0.3g (1.1mmol) of palladium acetate, 1.1g (1.1mmol) of triethylamine, heating Reflux for 15 hours, concentrate, column chromatography cyclohexane: ethyl acetate (volume ratio) = 5:2 mixed solvent as a developing solvent for separation and purification to obtain 2.34 g of the product with a yield of 60%.

Embodiment 3

[0027] Add 3.3g (10mmol) of dehydroepiandrosterone acetate, 2.5g (12mmol) of aluminum isopropoxide, 5mL of isopropanol, and 50mL of toluene into a 250mL three-neck flask, carry out the reduction reaction at 150°C for 5 hours, cool properly and add molecular sieves 3g, 9g of diatomaceous earth (as desiccant and decolorizer at the same time), heating and reflux dehydration, cooling and then adding 1.6g (11mmol) of 3-bromopyridine, 0.3g (1.1mmol) of palladium acetate, 1.1g (1.1mmol) of triethylamine) , heated to reflux for 15 hours, concentrated, column chromatography cyclohexane: ethyl acetate (volume ratio) = 5:2 mixed solvent as a developing solvent for separation and purification to obtain 2.4 g of the product, the yield was 61%.

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Abstract

The invention discloses a synthetic method of abiraterone acetic ester. The synthetic method is characterized by taking dehydro-epiandrosterone acetic ester shown by a formula (I) as a raw material, and performing reduction, dehydration and Heck coupling reaction to prepare abiraterone acetic ester shown by a formula (II). The synthetic method is easy to operate, is high in total yield and is a new synthesis technical route which is safe, and the raw material is easily-available to facilitate industrial production.

Description

technical field [0001] The invention relates to a synthetic method of abiraterone acetate. Background technique [0002] Abiraterone acetate (Abiraterone acetate), chemical name (3 β )-Acetoxy-17-(3-pyridyl)androst-5,16-diene, a prodrug of abiraterone. It was originally developed by the Institute of Cancer Research (ICR), and the British Technology Group (TheBritishTechnologyGroup, BTG) provided funding and developed clinical applications. The first phase of clinical trials was completed by Boehringer Ingelheim in Germany, and American Cougar Biotechnology Company undertook the work of the second and third phases of clinical trials. After Johnson & Johnson acquired Cougar Biotechnology in July 2009, Janssen Biotech Inc was responsible for the evaluation and marketing of Phase III clinical trials. Abiraterone acetate was approved for marketing by the U.S. FDA on April 28, 2011, under the trade name Zytiga. In July of the same year, the European Medicines Agency (EMA) appro...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J43/00
CPCC07J43/003
Inventor 朱建勋裴文尚军旗
Owner 浙江东晖药业有限公司