GB952193A - A process for the manufacture of steroid-21-orthophosphates and their salts - Google Patents

Abstract

Steroid 21-orthophosphates of the general formula: <FORM:0952193/C2/1> and their physiologically compatible water soluble salts are prepared by reacting steroid 21-amido-phosphates of the general formula: <FORM:0952193/C2/2> wherein R1 and R2 represent hydrogen atoms or organic radicals which may be linked together and St represents a steroid radical of the pregnane series with a free valency at the 21-position, with acidic reagents in the presence of a solvent and, if desired, converting the steroid 21-orthophosphates into the physiologically compatible water soluble inorganic or organic salts. Suitable acidic reagents are acid ion exchangers, mineral acids and strong organic acids such as sulphonic acids. The radicals R1 and R2 may be hydrogen, hydrocarbon radicals such as alkyl, aralkyl or aryl radicals which may be substituted and/or contain heteroatoms, or may be joined together to form a ring in which case the ring may contain hetero-atoms such as piperidine, pyridine or morpholine ring. The steroid radical may have oxygen functions in the 3-, 11-, 16-, 17- or 20-position, double bonds in the 1-, 4-, 1- and 4-, 4- and 6- or 1-, 4- and 6-positions or in the 9(11)-position. Double bonds in the 1- and/or 4- and/or 6-position may be formed by dehydrogenation following the above process, or an 11-hydroxy group may be oxidised to an 11-keto group. Halogen may also be present, for example, in the 9-, 6- or 2-position or a double bond in the 6(7) position and a halogen in the 6-position may be present. Alkyl groups may be present in the 2- and/or 6-positions, and an alkyl or alkylidene group may be present at the 16-position. The salts may be prepared with inorganic and organic bases such as caustic alkali, alkali carbonate, alkali metal hydrogen carbonate and ammonia, or with amines such as diethylamine or triethylamine. 21-Amido-phosphates of the second general formula above are prepared by reacting 21-hydroxy-steroids with reagents which are capable of forming 21-dihalogenophosphates such as phosphorus oxychloride or pyrophosphoryl chloride, and reacting the 21-dihalogenophosphates with amines, or by reacting 21-hydroxysteroids with diamidophosphoryl halogenides of the formula: <FORM:0952193/C2/3> or with tetra-amidopyrophosphates of the formula: <FORM:0952193/C2/4> wherein R1 and R2 have the above significance. Reference has been directed by the Comptroller to Specifications 805,828 and 826,365.