Continuous preparation process of 2 '-O-methyl-2-amino adenosine

Abstract

The invention provides a continuous preparation process of 2 '-O-methyl-2-amino adenosine, which comprises the following steps: (1) dissolving a substrate 2-amino adenosine and a catalyst Lewis acid in a first solvent to obtain a solution A, and dissolving a methylation reagent diazomethane in a second solvent to obtain a solution B; (2) enabling the solution A to enter a reactor through a pump A at a certain feeding speed, enabling the solution B to enter the reactor through a pump B at a certain feeding speed, adjusting the feeding speed so that the molar ratio of 2-amino adenosine to diazomethane is basically controlled to be 1: (1-1.25), controlling the temperature in the reactor to be 20-100 DEG C and the retention time of a reaction system in the reactor to be 15-30 minutes, receiving a reaction product through a discharge port, and obtaining the 2-amino adenosine diazomethane. And concentrating and crystallizing to obtain a 2 '-O-methyl-2-amino adenosine solid. By adopting a continuous diazomethane methylation method, continuous industrial production can be realized, the production time is greatly shortened, and the process is safe, stable and efficient.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, in particular to a continuous preparation process of 2'-O-methyl-2-aminoadenosine. Background technique [0002] 2'-O-methyl ribonucleosides are widely distributed in RNA and have been the focus of extensive synthetic work since the late 1950s. Especially the synthesis of 2'-O-methylguanosine is challenging. Through literature research, 2-aminoadenosine was directly methylated by methylation reagents such as methyl iodide or dimethyl sulfate, but the existence of 3'-O-methyl isomer complicates purification, Usually the yield is very low. If the 3'-O-methyl isomer is to be avoided, the expensive 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane reagent needs to be used, and the route needs at least two more step. With the rise of small nucleic acid drugs and the increasing demand for raw materials, the development of cost-effective 2'-O-methylguanosine synthesis methods has become more and more i...

AI Technical Summary

Problems solved by technology

Especially the synthesis of 2'-O-methylguanosine is challenging

Through literature research, 2-aminoadenosine was directly methylated by methylating reagents such as methyl iodide or dimethyl sulfate, but the existence of 3'-O-methyl isomers made the purification complicated. usually low yield

And if you want to avoid the 3'-O-methyl isomer, you need to use expensive 1,3 dichloro-1,1,3,3-tetraisopropyldisiloxane reagent, the route needs at least two more step

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