反应详情

A mixture of 10-bromo-3-(chloromethyl)-2-iodo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine (200 mg, 0.46 mmol, 1.00 equiv), 2-methyl-1H-1,3-benzodiazole (304 mg, 2.30 mmol, 5.00 equiv), Cs2CO3 (450 mg, 1.38 mmol, 3.00 equiv) in N,N-dimethylformamide (2 mL) was stirred overnight at room temperature. The reaction mixture was diluted with water, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (10:1). This resulted in 140 mg (57%) of 10-bromo-2-iodo-3((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine as a colorless solid. Similar to Example 10 (carbonylative amidation) a 20-mL sealed tube purged and maintained with an inert atmosphere of CO(g), was placed a solution of 10-bromo-2-iodo-3((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine (140 mg, 0.26 mmol, 1.00 equiv), HMDS (105 mg, 0.65 mmol, 2.50 equiv), Pd(dppf)Cl2 (21 mg, 0.10 equiv), and N,N-dimethylformamide (2 mL). The resulting solution was heated to 70° C. for 4 h and diluted with water. Then the resulting solution was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (10:1). This resulted in 90 mg (76%) of 10-bromo-3-((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide as a yellow solid. Similar to as described in General Procedure E with the exceptions of using Pd(PPh3)4 in DMSO, 10-bromo-3((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide was reacted with (R)-2-(5-methylisoxazol-3-yl)but-3-yn-2-ol to give the titled compound as a yellow solid (29 mg, 31%).

1. extractionextracted with ethyl acetate
2. dry with materialdried over anhydrous sodium sulfate
3. concentrationconcentrated under vacuum
4. customThis resulted in 140 mg (57%) of 10-bromo-2-iodo-3((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine as a colorless solid
5. customSimilar to Example 10 (carbonylative amidation) a 20-mL sealed tube
6. custompurged
7. temperaturemaintained with an inert atmosphere of CO(g)
8. temperatureThe resulting solution was heated to 70° C. for 4 h
9. extractionThen the resulting solution was extracted with ethyl acetate
10. dry with materialdried over anhydrous sodium sulfate
11. concentrationconcentrated under vacuum
12. customThis resulted in 90 mg (76%) of 10-bromo-3-((2-methyl-1H-benzo[d]imidazol-1-yl)methyl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide as a yellow solid