Process for Preparing Nucleoside-5<1>-Phosphoramidates.

摘要

1,171,873. Nucleoside - 51 - phosphoramidates. AJINOMOTO CO. Inc. 23 April, 1968 [25 April, 1967], No. 19213/68. Heading C2C. Nucleoside- and 21,31-o-protected nucleoside- 51-phosphoramidates are prepared by reacting a nucleoside- or 21,31-o-protected nucleoside-51- monochlorophosphate with ammonia or an amine in the presence of, as a solvent, a trialkyl or tri-(haloalkyl) phosphate. The nucleoside- or 21, 31-o-protected nucleoside-51-monochlorophosphate may be prepared by partial hydrolysis, e.g. with water of the corresponding dichlorophosphate, which, in turn, may be prepared by reacting a nucleoside or 21,31-oprotected nucleoside with phosphorus oxychloride or tetrachloropyrophosphate. Suitable protecting groups specified are acyl and alkylidene groups. An excess of ammonia or amine is used in the main process for the neutralization of the acid produced by the partial hydrolysis. Liquid or gaseous ammonia or a primary alkylamine or secondary dialkylamine, each alkyl group having up to 6 carbon atoms, aromatic or heterocyclic amine may be used in the main process. Examples describe the preparation of inosine- and uridine-51-phosphoromorpholidates; 21,31-o-isopropylidene-adenosine-, guanosine- and inosine-51-phosphoromorpholidates; adenosine- and 21,31-o-isopropylidene-adensoine- 51-phosphoramidates; and 5-amino-4-imidazolcarboxamide riboside-51-phosphoromorpholid. ate.