McPherson, Andrew K’s team published research in Organic Process Research & Development in 2020-11-20 | 6482-24-2

Organic Process Research & Development published new progress about Alkylation. 6482-24-2 belongs to class ethers-buliding-blocks, and the molecular formula is C3H7BrO, Category: ethers-buliding-blocks.

McPherson, Andrew K.; Capaldi, Daniel; Chen, Lijian; Olsen, Philip published the artcile< An Improved Process for the Manufacture of 5'-O-(4,4'-Dimethoxytrityl)-N2-isobutyryl-2'-O-(2-methoxyethyl)guanosine>, Category: ethers-buliding-blocks, the main research area is alkylation aminopurine riboside bromomethoxyethane nucleoside nucleotide preparation enzymic.

A revised, optimized process for the manufacture of 5′-O-(4,4′-dimethoxytrityl)-N2-isobutyryl-2′-O-(2-methoxyethyl)guanosine (MOE G PNS) that controls critical impurities to less than 0.2% was developed. The 2′-O-alkylation of 2,6-diaminopurine riboside (DAPR) with 1-bromo-2-methoxyethane (MOE-Br) in DMSO was examined using a DOE approach, which lead to the selection of LiOH as the optimal base choice. DMSO was removed with a solid-phase extraction using SP-207 resin, affording the desired 2′-O-(2-methoxyethyl)-2,6-diaminopurine riboside (MOE DAPR) in an aqueous solution in 53% yield. The methylbromide impurity commonly found in bulk source MOE-Br was controlled using a co-distillation with MEK, thereby controlling the resulting critical 2′-O-Me nucleoside impurity. The aqueous solution was telescoped into the enzymic conversion of MOE-DAPR to 2′-O-(2-methoxyethyl)guanosine (MOE G) using adenosine deaminase. MOE G purity is enhanced at this step due to enzymic selectivity and crystallization from the reaction mixture, which together significantly reduce levels of the 3′ MOE G isomer. The improved process was carried out at production-scale to afford 59 kg of MOE G PNS with no critical impurity over 0.2% in an overall yield of 26%.

Organic Process Research & Development published new progress about Alkylation. 6482-24-2 belongs to class ethers-buliding-blocks, and the molecular formula is C3H7BrO, Category: ethers-buliding-blocks.

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem