Hydrochloric Acid → HCID 178437082, compound

Participants

Reaction Conditions

Reaction Steps

Solid 6-bromo-1-(pentan-3-yl)-1H-imidazo[4,5-b]pyridin-2-ol (2.0 g, 7.04 mmol, 1.0 equiv), CuI (133 mg, 0.7 mmol, 0.1 equiv), and (Ph3P)2PdCl2 (491 mg, 0.7 mmol, 0.1 equiv) were added to a dry round bottom flask equipped with a stir bar. The flask was sealed and purged with nitrogen and DMF (30 mL), TMS-acetylene (4.22 mL, 8.45 mmol, 1.2 quiv), and triethylamine (4.9 mL, 35.2 mmol, 5.0 equiv) were added by syringe. The resulting mixture was heated to 100° C. for 30 min. After the reaction was allowed to cool, the mixture was concentrated in vacuo and then resuspended in EtOAc. The mixture was washed three times with water, twice with satd. aq. NaHCO3, and once with brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification by silica gel MPLC (7%-66% EtOAc/Hexanes) provided the silylated product, which contained triphenylphosphine oxide as a contaminant, was taken on directly into the deprotection. The solid was dissolved in a 1:1 mixture of THF:MeOH (30 mL), and solid KOH (1.97 g, 35.2 mmol, 5.0 equiv) was added in one portion. After 5 min, the reaction was diluted with water and acidified to pH 7 by the addition of 1 N HCl. The mixture was extracted with EtOAc, and the organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification by silica gel MPLC (10%-60% EtOAc/Hexanes) provided 6-ethynyl-1-(pentan-3-yl)-1H-imidazo[4,5-b]pyridin-2-ol as a white solid (713 mg, 45%). m/z=230.2 [M+H]+

Provenance & Evidence