Patent ID: 6335437
Filing Date: 2002-01-01
Classification: C07H

Abstract:
A method for the preparation of a conjugated oligonucleotide comprising:providing a compound of Formula I: wherein: R1 is a phosphorus protecting group; R2 is selected from the groups consisting of chlorine and a pendant group; R3 is selected from the group consisting of â€”N(R4)2, a heterocycloalkyl ring containing from 4 to 7 atoms, a heterocycloalkenyl ring containing from 4 to 7 atoms, said heterocycloalkyl and heterocycloalkenyl rings each having up to 3 heteroatoms selected from nitrogen, sulfur, and oxygen; R4 is straight or branched chain alkyl having from 1 to 10 carbons. v is 1 or 1; n is 1 to about 10; Q has one of the Formulas II or III: wherein: R5 is a hydroxyl protecting group; B is a nucleobase; R6 is selected from the group consisting of F, Oâ€”R20, Sâ€”R20 and Nâ€”R20(R21); R20 is alkyl, or a ring system having from about 4 to about 7 carbon atoms, or having from about 3 to about 6 carbon atoms and 1 or 2 hetero atoms, wherein said hetero atoms are selected from the group consisting of oxygen, nitrogen and sulfur and wherein said ring system is aliphatic, unsaturated aliphatic, aromatic and heterocyclic; and wherein any available hydrogen atom of said ring system is optionally replaced with an alkoxy, alkylamino, urea or alkylurea group; or R20 has one of the formulas: whereinQ1 is O, S or NR2; m is from 1 to 10; y is from 0 to 10; E is N(R21)(R31), N&boxH;C(R21)(R31), C1-C10 alkyl, or C1-C10 substituted alkyl wherein said substituent is N(R2)(R3); each R21 and R31 is, independently, H, C1-C10 alkyl, alkylthioalkyl, a nitrogen protecting group, or R2 and R3, together, are a nitrogen protecting group or wherein R2 and R3 are joined in a ring structure that can include at least one heteroatom selected from the group consisting of N and O; and R4, is H or C1-C12 alkyl;reacting said compound of Formula I with a compound of Formula IV: wherein: R7 is H, a hydroxyl protecting group, or a linker connected to a solid support; w is 0 to about 100; to form a compound of Formula IVa: andcontacting the compound of Formula IVa with a pendant group for a time and under conditions sufficient to form said conjugate.