5-Iodocytidine synthesis

Yield: 85.1%

Reaction Conditions:

with iodine;iodic acid;acetic acid in tetrachloromethane;water at 20 - 40;

Steps:

59; 60; 61 Synthesis of 5-iodocytidine 191:
Synthesis of 5-iodocytidine 191: A mixture of cytidine 190 (15.0 g, 61.7 mmol) in 225 mL of acetic acid and 225 mL of carbon tetrachioride was warmed to 40 CC, and iodine (9.6 g, 75.7 mmol) was added.To the stirred reaction mixture was added slowly a solution of iodic acid (9.6 g, 54.6 mmol) in 25 mL of water within 10 mm. The reaction mixture was stirred at 40 CC for 6 h and stirred at room temperature overnight. Upon completion of the reaction as monitored by TLC, the reaction mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column using dichloromethane-methanol(15:1 to 10:1 to5:1) asgradienteluents resulting in 19.4g (85.1%) desiredproduct 5-iodocytidine (191).

References:

MODERNA THERAPEUTICS, INC.;ROY, Atanu;CONLEE, Christopher, R.;DE FOUGEROLLES, Antonin;FRALEY, Andrew, W. WO2015/196130, 2015, A2 Location in patent:Page/Page column 634; 635