Synthesis method of 17-(3-pyridyl)-androst-4, 16-diene-3beta-ol acetate

Abstract

The invention discloses a synthesis method of 17-(3-pyridyl)-androst-4, 16-diene-3beta-ol acetate. The reaction route is shown as the following: preparing a Grignard reagent from isopropyl chloride and magnesium powder, and then conducting Grignard exchange with 3-bromopyridine to obtain a 3-bromopyridine Grignard reagent; in the presence of isopropyl ether as a solvent, adding dehydroepiandrosterone acetate to carry out condensation reaction, then adding a Burgess reagent to perform dehydration so as to obtain an Abiraterone acetate crude product; then carrying out hydrolysis to obtain 17-(3-pyridyl)-androst-4, 16-diene-3beta-ol and performing recrystallization; and then adding an acetylation reagent to carry out reaction so as to obtain the target compound. The method provided by the invention has the advantages of simple operation, cheap and easily available raw materials, mild reaction conditions, low equipment requirement and high total yield, synchronous recovery of the used solvent and the like, and is low in production cost and easy for large-scale production, thus having significant industrial application value.

Description

technical field [0001] The invention relates to nitrogen-containing steroidal compounds, in particular to a method for synthesizing 17-(3-pyridyl)-androst-4,16-dien-3β-alcohol acetate. Background technique [0002] Abiraterone acetate (Abiraterone acetate, the chemical name is 17-(3-pyridyl)-androst-4,16-dien-3β-ol acetate) is an orally effective androgen developed by the American centocoroftho company Biosynthesis inhibitor; in 2011, it was approved for marketing by the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency (EMEA), with the trade name Zytiga. The drug is clinically used in combination with prednisone (Prednisone) to treat metastatic advanced prostate cancer that has developed resistance to traditional hormone therapy. lives of cancer patients. Recently, the US Food and Drug Administration and the European Agency for Medicines Evaluation also approved the addition of abiraterone acetate, which can be used before chemotherapy in ...

AI Technical Summary

Problems solved by technology

In the process of preparing active sulfonate in this route, the raw materials are always incompletely reacted, and H-NMR monitoring is required, and diethyl-3-pyridine borane is expensive, which is not conducive to industrial production

[0007] In Chinese patent CN201210078438.2, abiraterone acetate is prepared by using dehydroepiandrosterone acetate to form a hydrazone, iodine and pyridine zinc reagent. In this route, the preparation of pyridine zinc reagent is complicated and the reaction conditions are harsh. Ultra-low temperature (-78°C), anhydrous and oxygen-free

Not conducive to industrial production

[0008] In summary, there are still many deficiencies in the synthesis route of abiraterone acetate involved in the current published literature reports, preparation cost, yield and waste removal, especially how to reduce reaction steps, improve chemoselectivity and Purification has important practical significance for the economic and technological development of abiraterone acetate raw materials

In addition, the abiraterone acetate prepared by the prior art has low purity and is difficult to be directly applied to pharmaceutical production

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