Synthesis of thiolated oligonucleotides without a capping step

A process for of preparing an oligonucleotide comprising

• a) reacting the compound of Formula (I):
• with the compound of Formula (II):
• to form a compound of Formula (III):
• and
• b) sulfurizing the compound of Formula (III) with a sulfurization agent to form a compound of Formula (IV):
• and from unreacted compound of Formula (I) forms a compound of Formula (V):
• wherein
• Each R1 and R11 are independently a nucleobase, wherein the NH2 of the nucleobase, if present, is protected by an amine protecting group;
• Each R2 and R12 are independently selected from the group consisting of H, halo, and C1-6alkoxy optionally substituted with C1-6alkoxy;
• R3 is a solid support, optionally comprising a linker;
• Y is absent, a nucleotide, or an oligonucleotide comprising 2 or more nucleotides;
• Each R4 is independently H or forms a ring with the alkoxy group of R2;
• Each R14 is independently H or forms a ring with the alkoxy group of R12;
• R15 is a hydroxy protecting group;
• R16 is C1-6alkyl optionally substituted with —CN;
• R17a and R17b are independently C1-6alkyl;
• RS is a hydroxy protecting group formed from a byproduct of the sulfurization agent;
• wherein the sulfurization agent is reacted for a sufficient amount of time to substantially completely convert unreacted compound of Formula (I) to the compound of Formula (V) and to convert the compound of Formula (III) to Formula (IV);
• wherein a sufficient amount of sulfurization agent is added to substantially completely convert unreacted compound of Formula (I) to Formula (V) and to convert the compound of Formula (III) to Formula (IV);
• and
• wherein the compounds of Formulas (I), (II), (III), (IV), and (V) are optionally in the form of a pharmaceutically acceptable salt.