Patent ID: 8299206
Filing Date: 2012-10-30
Classification: C08G,C08L

Abstract:
1. A method of synthesizing a morpholino oligomer, the method comprising: (a) reacting a solid-phase-supported morpholino subunit comprising an unprotected morpholino ring nitrogen with a first morpholino subunit monomer comprising a triarylmethyl-protected morpholino ring nitrogen and an activated phosphoramidate group on a 5′-exocyclic carbon, thereby forming a phosphorodiamidate linkage between the 5′-exocyclic carbon of the first morpholino subunit monomer and the unprotected morpholino ring nitrogen of the solid-phase supported morpholino subunit monomer; (b) deprotecting the triarylmethyl-protected morpholino ring nitrogen, to form a product comprising an unprotected morpholino ring nitrogen; (c) optionally reacting the product from step (b) with a further morpholino subunit monomer comprising a triarylmethyl-protected morpholino ring nitrogen and an activated phosphoramidate group on a 5′-exocyclic carbon, thereby forming a phosphorodiamidate linkage between the 5′-exocyclic carbon of the further morpholino subunit monomer and the unprotected morpholino ring nitrogen of the product from step (b); and (d) optionally repeating steps (b) and (c) one or more times; wherein the deprotecting comprises exposing the triarylmethyl-protected ring nitrogen to a reagent solution comprising a heterocyclic amine salt in a trifluoroethanol-containing solvent, the salt being a salt of a heterocyclic amine with a sulfonic acid, trifluoroacetic acid or hydrochloric acid and having a pKa in the range of 1-4 in its protonated form.