Sodium Carbonate → 6-((7S)-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-[(1S)-1,3-dihydroxy-1-(1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (1.0 g, 3.1 mmol) in tetrahydrofuran (100 mL) were added N-ethyldiisopropylamine (2.39 g, 18.4 mmol) and methanesulfonyl chloride (2.11 g, 18.4 mmol) at room temperature. The mixture was stirred at the same temperature for 3 hr. To the reaction mixture was added a solution of sodium carbonate (1.31 g, 12.3 mmol) in water (3 mL). The mixture was heated to 60° C. and stirred for 5 hr. After the reaction mixture was allowed to cool to room temperature, ethyl acetate (25 mL) was added thereto. The organic layer was separated and concentrated under reduced pressure. Methanol (16.7 mL) and water (6.4 mL) were added to the residue. The mixture was heated to 65° C., and activated carbon (45 mg) was added thereto. After stirring at the same temperature for 30 min, the activated carbon was filtered off and washed with methanol (1.1 mL). Water (6.4 mL) was added to the filtrate at 55° C. The resulting mixture was allowed to cool to room temperature and stirred for 30 min. To the mixture was added water (6.4 mL) at the same temperature, and the mixture was stirred for 2 hr. The mixture was cooled to 0° C. and stirred for 2 hr. The obtained precipitated crystals were collected by filtration, washed with 45% aqueous methanol (3 mL), and dried under reduced pressure to give 6-((7S)-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide (540 mg, 1.8 mmol). yield 57%.

Provenance & Evidence