2-Methyl-3-butyn-2-ol → 10-(3-Hydroxy-3-methylbut-1-yn-1-yl)-3-(pyrrolidin-1-ylmethyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

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Reaction Steps

10-bromo-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine (300 mg, 0.77 mmol, 1.00 equiv), HCHO/H2O (312 mg, 4.00 equiv), pyrrolidine (332 mg, 4.67 mmol, 6.00 equiv) in acetic acid (4 mL) was stirred overnight at 55° C. The resulting solution was diluted with dichloromethane, washed with saturated aqueous NaHCO3 solution, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/MeOH (10/1). This resulted in 200 mg of 10-bromo-2-iodo-3-(pyrrolidin-1-ylmethyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineas yellow oil that was used without further purification or characterization. Similar to as described in Example 10 (carbonylative amidation), a solution of this intermediate (200 mg, 0.42 mmol, 1.00 equiv), HMDS (135 mg, 0.84 mmol, 2.00 equiv), Pd(dppf)Cl2(34 mg, 0.05 mmol, 0.10 equiv) in N,N-dimethylformamide (2 mL) was stirred overnight at 70° C. under an atmosphere of CO (g). The resulting solution was diluted with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (1:10). This resulted in 80 mg (48%) of 10-bromo-3-(pyrrolidin-1-ylmethyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide as a yellow solid. Similar to as described in General Procedure G, 10-bromo-3-(pyrrolidin-1-ylmethyl)-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 yellow solid (14 mg, 18%).

Provenance & Evidence