Sodium Iodide → HCID 16725698, compound

Participants

Reaction Conditions

Reaction Steps

A thick-walled pressure vessel was charged with 1,1-dimethylethyl 2-({[2-(4-amino-1,2,5-oxadiazol-3-yl)-4-chloro-1-ethyl-1H-imidazo[4,5-c]pyridin-7-yl]oxy}methyl)-4-thiomorpholinecarboxylate (enantiomer E1) (0.18 g, 1.35 mmol), Zn dust (0.03 g, 0.40 mmol), NaI (0.06 g, 0.40 mmol), DBU (0.61 mL, 4.00 mmol), TEA (0.56 mL, 4.00 mmol), 2-methyl-3-butyn-2-ol (0.48 mL, 5.70 mmol), (Ph3P)4Pd (0.08 g, 0.08 mmol) and dioxane (35 mL). After purging the mixture with nitrogen for 10 min., the vessel was sealed and heated at 80° C. for 2.5 h. After allowing the reaction to cool to ambient temperature, sat NH4Cl was added and the reaction was extracted with EtOAc. The combined organic extracts were washed with water, brine and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue subjected to flash chromatography (MeOH/CH2Cl2, silica gel). The Boc-protected product was dissolved in 25% TFA/CH2Cl2 (10 mL). After 30 min., the solvent was removed under reduced pressure. The residue was partitioned between 1N NaOH and ethyl acetate. The aqueous layer was extracted with additional ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate. The solvent was removed under reduced pressure. Flash chromatography (MeOH/CH2Cl2, silica gel) gave 0.22 g (37% yield) of the desired compound. MS (ES+) m/z 444 (M+H)+.

Provenance & Evidence