Patent ID: 8304532

Claim:
A method comprising the steps of, in a first cycle, a) providing a first compound having the formula: wherein B is a nucleobase, Y is H or forms a C4′-O2′ methylene linkage with R 2 , R 2 is H, a protected 2′-hydroxyl group, F, a protected amino group, an O-alkyl group, an O-substituted alkyl, a substituted alkylamino, or forms a C4′-O2′ methylene linkage with Y, R 3 is OR′ 3 , NHR″ 3 , NR″ 3 R′″ 3 , a 3′-protected 5′-nucleotidyl group, or a 3′-protected 5′-oligonucleotidyl group, R′ 3 is a hydroxyl protecting group, and R″ 3 , R′″ 3 are independently an amine protecting group; b) providing a second compound having the formula: wherein X comprises a P(III) phosphorus atom, Y is H or forms a C4′-O2′ methylene linkage with R 2 , B is a nucleobase, R 2 is H, a protected 2′-hydroxyl group, F, a protected amino group, an O-alkyl group, an O-substituted alkyl, a substituted alkylamino or a C4′-O2′ methylene linkage, and R 5 is a hydroxyl protecting group, a 5′-protected 3′-nucleotidyl group, or a 5′-protected 3′-oligonucleotidyl group; c) reacting the first compound with the second compound in the presence of a solid supported activator to produce 3′-5′-protected elongated oligonucleotide comprising an internucleotide linkage comprising a P(III) phosphorus atom; d) optionally modifying the 3′-5′-protected elongated oligonucleotide by either or both of steps d1) and d2) in any sequence: d1) reacting the 3′-5′-protected elongated oligonucleotide with a solid supported capping reagent; d2) reacting the 3′-5′-protected elongated oligonucleotide with a solid supported oxidizing reagent to provide an internucleotide linkage comprising a P(V) phosphorus atom; e) removing the 5′-protection group by reacting the 3′-5′-protected elongated oligonucleotide with (i) a solid supported deprotection reagent or (ii) a deprotection reagent followed by addition of a solid supported scavenger, to produce a 3′-protected elongated oligonucleotide; and f) in a second cycle, repeating steps a) to e) wherein the first compound provided in step a) of the second cycle is the 3′-protected elongated oligonucleotide of step e) of the first cycle.