Verfahren zur Herstellung von Fluorpyrimidinen

摘要

The invention comprises compounds of the formula in which R is a hydroxy or amino group, R1 is a hydrogen atom or a C1-4 alkyl or C2-4 acyl group, X is a halogen atom and the bond shown as a broken line indicates that the substituent attached thereby is optional. The compounds may be prepared by additively reacting a 4-substituted 2-oxo-5-fluoro-pyrimidine of the formula with an agent yielding the atom X and the radical OR1, e.g. a hypohalous acid or a C1-4 alkyl ester thereof, and, if desired, dehalogenating the resulting compound of the formula to yield the corresponding compound in which the substituent X is absent. The agent yielding the atom X and the radical OR1 may be prepared in situ. The 6-alkoxy or 6-acyloxy compounds may also be prepared by etherification or esterification, respectively, of the corresponding 6-hydroxy compounds. The 6-butoxy compounds may also be prepared by reacting the corresponding methoxy compound with a butanol in the presence of a catalyst, e.g. HBr. The optically active forms of the compounds of the invention may be prepared by oxidation of the optically active forms of the corresponding l-nucleosides. Dehalogenation of compounds of the formula III may be carried out by means of chemical reducing agents, e.g. on alkali metal hydrosulphide, or by catalytic hydrogenation. Pharmaceutical compositions for enteral or parenteral administration comprise a compound of the invention together with a pharmaceutical carrier. The compositions, which have germicidal, antimetabolic and antineoplastic activity, may be formulated as tablets, dragees, suppositories, capsules, solutions, suspensions or emulsions.