METHOD OF PRODUCING AMIDOPHOSPHITE MONOMER OF ACHIRAL NON-NUCLEOTIDE INSERT FOR MODIFYING OLIGONUCLEOTIDES Russian patent published in 2012 - IPC C07C231/02 C07H21/00 C12N15/09 

FIELD: chemistry.

SUBSTANCE: method of producing an aminophosphite monomer of an achiral non-nucleotide insert for modifying oligonucleotides involves dimethoxytritylation of the corresponding alcohol, branching the skeleton of the insert by reacting an amine with an activated carboxylic acid and phosphitylation of the precursor of the end compound in standard conditions. The first step involves synthesis of 4-(2-hydroxyethyl)morpholine-2,3-dione (compound I) by adding diethanolamine solution to a solution of diether of oxalic acid in molar ratio of diether of oxalic acid to diethanolamine equal to 1:1.15, while stirring at room temperature for 15-24 hours. Further, the obtained compound I is dimethoxytrirylated with dimethoxytritylchloride in equimolar ratio of reactants. The obtained compound II is then used for acylation of an aliphatic primary or secondary amine bearing the required functional group(s), at concentration of reactants of 0.1-0.4 M at temperature 25-60°C for 8-24 hours, followed by phosphitylation of the obtained compound 2-cyanoethyl-N,N,N',N' with tetraisopropyl diamidophosphite using a standard method to obtain the end amidophosphite monomer of an achiral non-nucleotide insert.

EFFECT: high output.

4 cl, 4 dwg, 4 tbl, 5 ex