Method for preparing atosiban acetate

摘要

The present invention provides a method for preparing atosiban acetate. The method comprises the following steps of: synthesizing to obtain linear atosiban; dissolving the linear atosiban in an acetonitrile aqueous solution, adjusting the pH value with ammonia water, adding H2O2 for oxidizing, filtering, purifying, and transferring salt to obtain the atosiban acetate. In the present invention, an appropriate route is provided, the linear atosiban is synthesized by adopting a solid phase method, and the atosiban is obtained by liquid phase oxidation. The method has the advantages of capabilities of solving the problem of insolubility of the linear atosiban, reducing the reaction size to the maximum extent and shortening reaction time, and being high in yield and easy to industrialize.

主权项

1. A method for preparing atosiban acetate, comprising the following steps of:
1) synthesizing linear atosiban by solid-phase synthesis method using Rink amide resin with a coupling agent, wherein the coupling agent can be chosen from DIC/HOBt, yBOP/HOBt, HATU/HOBt or HBTU/HOBt; and 2) dissolving the linear atosiban with 5-15% acetonitrile aqueous solution, wherein the molar ratio of linear atosiban to H2O2 is 1:2-8, concentration of linear atosiban is 0.01-0.03 g/ml, through the following steps:
a) adjusting the pH to 8-9 with ammonia water,b) oxidizing with H2O2, during oxidizing with H2O2 the oxidizing time is 5-60 min and the oxidizing reaction temperature is 10-40° C.,c) filtering through diatomite to obtain crude filtrate and micro-filtering through microporous filter membrane to obtain micro-filtrate,d) purifying by RP-HPLC, ande) transferring salt to obtain the atosiban acetate.