SYNTHESIS OF OLIGONUCLEOTIDES OR PHOSPHOROTHIOATE OLIGONUCLEOTIDE WITH A CAPPING AGENT OF N-METHYLIMIDAZOLE FREE OF 1,3,5-TRIMETHYLHEXAHYDRO-1,3,5-TRIAZINE

摘要

According to the present invention, there is provided a process for making an oligonucleotide or a phosphorothioate oligonucleotide. The process has the following steps: (a) providing an amount of a blocked nucleotide; (b) deblocking the blocked nucleotide to form an unblocked nucleotide; (c) activating the deblocked nucleotide; (d) coupling the deblocked nucleotide with a phosphoramidite to form a phosphite oligomer; (e) capping any uncoupled deblocked nucleotide via reaction with an amount of acetic anhydride and an amount of N-methylimidazole that is substantially free of 1,3,5-trimethylhexahydro-1,3,5-triazine; (f) oxidizing the phosphite oligomer to form the oligonucleotide or sulfurizing the phosphite oligomer to form a phosphorothioate oligonucleotide; and (g) optionally repeating steps (b) through (f). There is also a process for capping a nucleotide.