Process for the preparation of oligonucleotide compounds

A method of preparing an oligomeric compound of formula:

• wherein:
• T5 is H, a hydroxyl blocking group, a nucleoside, an oligonucleoside, a nucleotide an oligonucleotide or a conjugate group;
• T6 is H, a hydroxyl protecting group, a nucleoside, an oligonucleoside, a nucleotide an oligonucleotide or a conjugate group;
• mm is from about 5 to about 50;
• each Xa is, independently, O or S;
• each Xb is, independently, OH, SH or NRaRb;
• each Ra and Rb is, independently, H, a nitrogen protecting group, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl, wherein said substitution is by hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl or alkynyl;
• Bxx is a purine or purine analog;
• each Bx is, independently, an optionally blocked heterocyclic base moiety;
• each R is, independently, hydrogen or an optionally protected substituent group;
• L is a bifunctional linking moiety having the formula —C(═O)—(CH2)nn—C(═O)— where nn is from 4 to 25;
• and
• SM is a support medium;
• comprising the steps of:
• (a) providing a compound of the formula:
• wherein:
• T1 is a 5′-hydroxyl protecting group;
• (b) removing said 5′-hydroxyl protecting group to form a deprotected hydroxyl group by contacting same with a reagent effective to remove said protecting groups;
• (c) treating said deprotected hydroxyl group with a further compound having the formula:
• wherein:
• T4 is a phosphoramidite;
• and an activating agent for a time and under conditions effective to form an extended oligomeric compound;
• d) treating said extended oligomeric compound with a capping agent to form a capped compound;
• e) treating said capped compound with an oxidizing agent;
• and
• f) optionally repeating steps b through e one or more times to form said oligomeric compound.