Patent ID: 6335439
Filing Date: 2002-01-01
Classification: C07H

Abstract:
A method for the preparation of a phosphoramidite having the Formula: wherein:R1 is a hydroxyl protecting group; B is a nucleobase; M is an internucleotide linkage; q is 1 to about 100; Z is H, OH, F, or a group of formula R7â€”-(R8)n; R7 is C3-C20 alkyl, C4-C20 alkenyl, C2-C20 alkynyl, C1-C20 alkoxy, C2-C20 alkenyloxy, or C2-C20 alkynyloxy; R8 is hydrogen, amino, halogen, hydroxyl, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, or polyether; n is from 0 to about 10; R3 is a group of formula â€”N(R5)(R6); R5 and R6 are independently alkyl having from one to four carbon atoms, or R5 and R6 taken together with the nitrogen atom to which they are attached form an aliphatic or aromatic five or six membered ring; R4 is a phosphorous protecting group; comprising: providing a solution consisting of a compound of Formula I: in a solvent; reacting the compound of Formula I in the solvent with a diaminohalophosphine of Formula: wherein X is halogen; and R2 is a group of formula â€”N(R5)(R6) to produce a reaction mixture containing a phosphordiamidite of Formula II: wherein the constituent variables are as defined previously; andcontacting the reaction mixture containing the compound of Formula II with a reagent of Formula R4â€”OH to produce the phosphoramidite.