Patent ID: 7105666

Claim:
A method for producing a substituted purine compound of the formula: wherein R 1 is a solid support, hydrogen, alkyl, cycloalkyl, or aryl; R 2 is alkyl, cycloalkyl, aryl, or a nitrogen protecting group; R 3 is hydrogen, alkyl, cycloalkyl, aryl, or a nitrogen protecting group; R 4 is hydrogen, alkyl, aryl, or NR 6 R 7 , where each of R 6 and R 7 is independently hydrogen, alkyl, aryl, or cycloalkyl; and R 5 is alkyl, alkoxy, alkenyl, alkynyl, aryl, aryloxy, cycloalkyl, cycloalkoxy, alkylthio, arylthio, or —NR 8 R 9 , where each of R 8 and R 9 is independently hydrogen, alkyl, cycloalkyl, aryl, or a nitrogen protecting group, or R 8 and R 9 together with the nitrogen atom to which they are attached to form heterocycle nonaromatic cyclic moiety of 3 to 8 atoms in which one ring atom is a nitrogen and a second ring atom is optionally a NR 10 (where R 10 is hydrogen or C 1-6 alkyl), O or S(O) n (where n is an integer from 0 to 2), the remaining ring atoms being C, where one or two C atoms may be optionally replaced by a carbonyl group; said method comprising: (a) contacting a 4,6-dihalo-5-nitro-2-thioether pyrimidine of the formula wherein R 10 is alkyl, cycloalkyl, or aryl and each X is independently halide: with a first amine compound of the formula HNR 1 R 2 to produce a 6-aminopyrimidine of the formula: (b) contacting the 6-aminopyrimidine with a second amine compound of the formula H 2 NR 3 to produce a 4,6-diaminopyrimidine of the formula: (c) contacting the 4,6-diamino pyrimidine with an oxidizing agent to produce a 2-sulfonylpyrimidine of the formula: (d) contacting the 2-sulfonylpyrimidine with a nucleophile of the formula R 5 -M wherein M is hydrogen, alkali metal, copper, or a R 5 -M is a Grignard reagent, to produce a 5-nitropyrimidine compound of the formula, (e) contacting the 5-nitropyrimidine compound with a reducing agent to produce a 4,5,6-triaminopyrimidine of the formula: and, (f) forming a purine ring by contacting the 4,5,6-triaminopyrimidine with a cyclizing agent to produce the substituted purine compound.