Patent ID: 9605019
Date: 2017-03-28
CPC Classifications: A61K,C07C,C07D,C07H

Claim:
1. A process for the preparation of an oligonucleotide of structure IIIa comprising the steps of: i) reacting an H-phosphonate of structure Ia with a silylating reagent to provide a silyloxyphosphonate; and ii) reacting the silyloxyphosphonate with a thiosulfonate reagent of structure IIa to provide an oligonucleotide of structure IIIa; wherein: the H-phosphonate of structure Ia has the following structure: wherein: W is O; R Y R R each instance of R each instance of R Y each instance of R each instance of Ba is independently a blocked or unblocked adenine, cytosine, guanine, thymine, uracil or modified nucleobase; R n is between 1 and about 200; and the thiosulfonate reagent of structure IIa has the following structure: wherein: X is alkyl, cycloalkyl, or heteroaryl; R is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, or R R R and the oligonucleotide of structure IIIa has the following structure: wherein: W is O; R is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, or R R R R Y R R each instance of R each instance of R Y each instance of R each instance of Ba is independently a blocked or unblocked adenine, cytosine, guanine, thymine, uracil or modified nucleobase; R n is between 1 and about 200; and wherein each heteroaryl group is a mono-, bi-, or poly-cyclic 5-14 membered ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur.