Patent ID: 6194576
Filing Date: 2001-02-27
Classification: C07H

Abstract:
A process for producing a compound of formula (I): ##STR181##whereinn is 0 or an integer,X is O, S, CH.sub.2, CH-halogen, CH--N.sub.3 or C.dbd.CH.sub.2 ;Q is CH.sub.2 ;U is O or S;Z is selected from: --O--, --O--C.sub.1-6 alkylene, --S--C.sub.1-6 alkylene, --NH--C.sub.1-6 alkylene, --(CH.sub.2).sub.m -- wherein m is from 0 to 6, and --NH--C.sub.1-6 wherein R.sub.c is hydrogen or a C.sub.1-6 alkyl; andR.sub.2 is a purine or pyrimidine nucleotide base or an analogue,wherein R.sub.2 is selected from the group consisting of: ##STR182##wherein:x is oxygen or sulfur;y is oxygen or sulfur;R.sub.3 and R.sub.4 are independently selected from the group consisting of hydrogen, hydroxyl, amino, C.sub.1-6 alkyl or C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-10 carboxylic-acid-acyl, aryl or carboxyl;R.sub.5, R.sub.6, R.sub.11, and R.sub.12 are each independently of the group consisting of hydrogen, halogen, hydroxyl, amino, cyano, carboxy, carbamoyl, alkoxycarbonyl, hydroxymethyl, trifluoromethyl, --S-aryl, C.sub.1-6 alkyl, C.sub.2-6 alkenyl substituted or unsubstituted with halogen or azido, C.sub.2-6 alkynyl, C.sub.1-10 carboxylic-acid-acyloxy, --S--COOH, --S-carbamoyl, carbamate, ureido, amidino, or aryloxy; and ##STR183##wherein;R.sub.7, R.sub.8, R.sub.9, and R.sub.10 are each independently selected from the group consisting of hydrogen, hydroxy, alkoxy, thiol, --S-alkyl, amino, substituted amino, halogen, azido, cyano, carboxy, alkoxycarbonyl, carbamoyl, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, or C.sub.2-6 alkynyl, C.sub.1-10 carboxylic-acid-acyloxy, aryl, aryloxy, --S--COOH, --S-carbamoyl, carbamate, ureido, amidino, and aryloxy,said process comprising:a) coupling an intermediate of formula (IIf): ##STR184##wherein n, m and X are as defined above;Y is O or S;R.sub.v is a hydroxy protecting group; andW is a displaceable group or a hydroxy group;with a purine or pyrimidine base, or analogue thereof as defined for R.sub.2 above to yield an ester of formula (I), andb) optionally, converting said ester to obtain a phoshonate derivative of formula (I).