Methyl iodide → 1-(2,2-Dimethylpropyl)-5-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Participants

Reaction Conditions

Reaction Steps

Diethyl zinc (0.53 mL, 0.53 mmol, 2.0 equiv, 1M in hexanes) was added to anhydrous DCM (0.53 mL) and cooled to 0° C. To this solution was added TFA (41 μL, 0.53 mmol, 2.0 equiv) in anhydrous DCM (0.27 mL), and the resulting mixture was stirred at 0° C. for 15 min. Following this duration, iodomethane (43 μL, 0.53 mmol, 2.0 equiv) in anhydrous DCM (0.27 mL) as added and the resulting reaction mixture was stirred for and additional 20 min. 1-(2,2-Dimethylpropyl)-5-[(1E)-4-hydroxybut-1-en-1-yl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (32-3, 77 mg, 0.27 mmol, 1.0 equiv) in anhydrous DCM (0.27) as then added. After 1 h, the reaction vessel was removed from the 0° C. bath and allowed to gradually warm to RT. After 2.5 h, LCMS showed consumption of 32-3. The reaction was quenched with saturated NH4Cl (5 mL) and extracted with ethyl acetate (3×5 ml). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give 32-4 as a white solid. Since the material was determined to be of >95% purity by 1H NMR, further purification was deemed unnecessary. MS m/z (M+H): calculated=303.4; observed=304.1.

Provenance & Evidence