High-purity (2 beta, 3 alpha, 5 alpha, 16 beta, 17 beta)-2-(4-morpholinyl)-16-(1-pyrrolidinyl)-androstane-3,17-diol or composition thereof and preparation method thereof

Abstract

The invention relates to a high-purity (2 beta, 3 alpha, 5 alpha, 16 beta, 17 beta)-2-(4- morpholinyl)-16-(1-pyrrolidinyl)-androstane-3,17-diol or a composition thereof, a preparation method thereof (a compound shown in a formula III) or a composition thereof and application thereof to preparing rocuronium (a compound shown in a formula I). The method has good effect, low cost, high quality and simple and convenient operation and is suitable for large-scale industrial production; and the obtained product has high purity and stable properties.

Description

technical field [0001] The invention relates to the technical fields of organic chemistry and medicinal chemistry, in particular to high-purity (2β, 3α, 5α, 16β, 17β)-2-(4-morpholinyl)-16-(1-pyrrolidinyl)-androstane -3,17-diol or its high-purity composition, its preparation method, and its application in the preparation of muscle relaxant rocuronium bromide. Background technique [0002] Muscle relaxants, also known as skeletal muscle relaxants (referred to as muscle relaxants), are also known as neuromuscular blocking agents, which selectively act on neuromuscular junctions, temporarily interfering with the transmission of excitement between neuromuscular and relaxing skeletal muscles drug. Muscle relaxants can be classified according to their mechanism of action into non-depolarizing and depolarizing muscle relaxants. Non-depolarizing muscle relaxants mainly act on the acetylcholine receptors on the post-synaptic membrane of the neuromuscular junction, compete with acety...

AI Technical Summary

Problems solved by technology

This method has increased acidic catalyst, quickened reaction process, but also caused reaction selectivity to reduce, and isomer impurity increases, and is not easy to be removed by the refining method of having reported, and operates according to its given condition, can not obtain The said yield (about 80%) of this patent, actual yield can only reach about 60%

[0012] The compound of formula III reacts with the acetylating reagent under the presence of an acylation reaction with an acetylating agent, and then obtains the compound of formula IV through two recrystallizations, but the process yield is low and the operation is complicated; the compound of formula IV forms a salt with allyl bromide Obtain formula I compound (rocuronium bromide)

[0013] In 2007, CN101381390 also improved the preparation method of the compound of formula III reported in US4894369 by reacting in an autoclave at 115-210°C for 36 hours and refining with methanol with a yield of 75%. The patent did not check the purity of the compound of formula III illustrate

[0014] Therefore, in the existing technology for the preparation of compounds of formula III, there are defects such as low product purity and lack of control of individual impurities, especially isomer impurities; thus causing subsequent reactions to require column chromatography and recrystallization purification, not Conducive to the improvement of operation and yield

For the deficiencies in the prior art, we compound (2β, 3α, 5α, 16β, 17β)-2-(4-morpholinyl)-16-(1-pyrrolidinyl)-androstane-3,17 The purification method of diol (compound of formula III) and the impurity control in the product have been studied, and it is found that there are mainly 4 kinds of impurities that have a great influence on the subsequent process

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