2-Methyl-3-butyn-2-ol → 10-(3-hydroxy-3-methylbut-1-yn-1-yl)-3-((2-methyl-1H-imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

Participants

Reaction Steps

Di-tert-butyl azodicarboxylate (470 mg, 1.79 mmol, 1.50 equiv) in tetrahydrofuran (2 mL) was added dropwise to a stirred solution of (10-bromo-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-3-yl)methanol (500 mg, 1.19 mmol, 1.00 equiv)), 2-methyl-1H-imidazole (200 mg, 2.44 mmol, 2.00 equiv), and triphenylphosphine (400 mg, 1.74 mmol, 1.50 equiv) in tetrahydrofuran (3 mL) at 0° C. under nitrogen. The resulting solution was stirred for 3 h at room temperature and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (10:1). This resulted in 260 mg (45%) of 10-bromo-2-iodo-3-((2-methyl-1H-imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineas as a colorless solid. This intermediate was converted to 10-bromo-3-((2-methyl-1H-imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide similar to as described in Example 10 (carbonylative amidation). Similar to as described in General Procedure G, 10-bromo-3((2-methyl-1H-imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide was reacted with 2-methylbut-3-yn-2-ol to give the titled compound as a colorless solid (2 mg, 2%).

Provenance & Evidence