4-Methylmorpholine → Ethyl 2-{(1R,5R)-2-[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]-2,6-diazabicyclo[3.2.0]hept-6-yl}-4-methyl-1,3-thiazole-5-carboxylate

Participants

Reaction Steps

WSC hydrochloride (377 mg, 1.97 mmol), 1-hydroxybenzotriazole (97 mg, 0.72 mmol) and N-methylmorpholine (0.14 mL, 1.31 mmol) were added to a mixed solution of ethyl 2-[(1R,5R)-2,6-diazabicyclo[3.2.0]hept-6-yl]-4-methyl-1,3-thiazole-5-carboxylate obtained in Example (236c) (175 mg, 0.66 mmol) and 4-chloro-5-ethyl-1H-imidazole-2-carboxylic acid obtained in Example (1d) (137 mg, 0.79 mmol) in DMA/dichloromethane (4 mL/4 mL), and the mixture was stirred at room temperature for 19 hours. The reaction solution was diluted with ethyl acetate, and then the mixture was washed with 5% saline and dried over anhydrous magnesium sulfate. Following filtration, the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=2/1) to obtain 192 mg of the title compound as a milk white solid (69%).

Provenance & Evidence