Methyl(2S)-2-[2-({[2-(but-3-en-1-yloxy)-5-fluorophenyl]methyl}carbamoyl)-7-methyl-5-[4-methyl-4-(prop-2-en-1-yloxy)piperidin-1-yl]imidazo[1,2-a]pyridin-6-yl]-2-(tert-butoxy)acetate → Methyl(2S)-2-(tert-butoxy)-2-{15-fluoro-4,26-dimethyl-10-oxo-19,25-dioxa-1,7,11,31-tetraazapentacyclo[24.2.2.16,9.02,7.013,18]hentriaconta-2,4,6(31),8,13(18),14,16-heptaen-3-yl}acetate

Participants

Reaction Steps

A solution of methyl(2S)-2-[2-({[2-(but-3-en-1-yloxy)-5-fluorophenyl]methyl}carbamoyl)-7-methyl-5-[4-methyl-4-(prop-2-en-1-yloxy)piperidin-1-yl]imidazo[1,2-a]pyridin-6-yl]-2-(tert-butoxy)acetate (0.046 g, 0.071 mmol, 1 equiv) and TsOH monohydrate (15 mg, 0.077 mmol, 1.1 equiv) in DCE (24 mL) was heated to 75° C. The Hoveyda Grubbs 2nd generation catalyst (9 mg, 0.014 mmol, 0.2 equiv) was added. The pale green brown solution was stirred for 1 h. Upon cooling to ambient temperature, the reaction was concentrated in vacuo. The residue was taken up in MeOH (5 mL) and 10% Pd/C (15 mg, 0.014 mmol, 0.2 equiv) was added. The reaction was then stirred under a balloon of H2 for 2 h. The reaction was then filtered through Celite eluting with MeOH. The filtrate was then concentrated in vacuo. The residue was taken up in DCM and washed with 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 (22 mg, 50%) as a brown film. LCMS (ESI, M+1): 625.35.

Provenance & Evidence