Dimethylformamide → (S)-Methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(5-(2-(but-3-en-1-yloxy)benzyl)-1,3,4-oxadiazol-2-yl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate

Participants

Reaction Conditions

Reaction Steps

A solution of (S)-5-(4-(allyloxy)-4-methylpiperidin-1-yl)-6-(1-(tert-butoxy)-2-methoxy-2-oxoethyl)-7-methylimidazo[1,2-a]pyridine-2-carboxylic acid sodium salt (76 mg, 0.153 mmol, 1 equiv), 2-(2-(but-3-en-1-yloxy)phenyl)acetohydrazide, HCl (55 mg, 0.214 mmol, 1.4 equiv), DIPEA (0.080 mL, 0.459 mmol, 3 equiv), and HATU (43 mg, 0.113 mmol, 1.4 equiv) in DMF (1.5 mL) was stirred 1 h. The reaction was then added to saturated aqueous NaHCO3 and extracted with DCM (×3). The combined DCM extracts were dried (Na2SO4), and concentrated in vacuo. The crude coupling product was taken up in THF (1.5 mL) and Burgess reagent (146 mg, 0.612 mmol, 4 equiv) was added. The reaction was then heated to 60° C. for 1.5 h. Upon cooling to ambient temperature, the reaction was diluted with DCM and washed with water, saturated aqueous NaHCO3, dried (Na2SO4), and concentrated in vacuo. The crude product was purified by flash column chromatography (0-100% EtOAc [2% TEA]/hexane) to provide the product (27 mg, 27%) as a yellow film. LCMS (ESI, M+1): 658.35.

Provenance & Evidence