Yield:80791-87-3 61 %

Reaction Conditions:

with sodium methylate in N,N-dimethyl-formamide at 20 - 100;Reagent/catalyst;

Steps:

1-5; 1-2

Add 10g of 2-amino-adenosine (35.46mmol) and 150mL DMF to a 500mL four-mouth bottle, raise the temperature to 90~100 °C and stir to dissolve the solid. When the solids are dissolved in DMF, naturally cool down to 20 °C, add 2.1g of sodium methoxide (38.89mmol), and stir for 15min. Then 2.2 mL of methyl iodide (35.35 mmol) is diluted with 50 mL DMF and added to the four-mouth vial at a drop acceleration of 5 mL/min. After dropping, the reaction is 2h. TLC detection (developing agent: 10% methanol/DCM), the reaction raw material reaction is complete. The HPLC of the reaction solution (Figure 1) showed that the 2-amino-2'-O-methyladenosine content was 66.9%. The reaction solution was cooled to -10 °C and 10 mL of methanol was slowly added dropwise. After dropwise addition, vacuum distillation is carried out in a 60°C water bath, and after distillation until there is almost no solvent distillation, the distillation is stopped by pressure relief. Add 100mL of ethyl acetate to dissolve the distilled material, stir and scatter for 1h, filter out the white solid insoluble in ethyl acetate, redissolve the solid in 50mL of ethanol, and white solid precipitate after stirring for 5h. Filtration, rinse the filter cake with 50mL of ethanol, add 120mL DMF to the obtained filter cake to dissolve, in a 60 °C water bath, evaporate the solvent under reduced pressure, add 50mL of methanol to dissolve, and crystallize for 5h. After filtration and drying, 6.4g of solid was obtained, the yield was 61.0%, and the purity of HPLC (Figure 2) was 99.3%.

References:

CN115651047,2023,A Location in patent:Paragraph 0036-0049