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

Temperature

10 °C

To THF (100 mL) and water (63 μg, 3.5 mmol) was added 6-[(1S)-1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (10.0 g, 17.6 mmol). The reaction mixture was cooled to 10° C., and ethyldiisopropylamine (3.41 g, 26.4 mmol) and methanesulfonyl chloride (3.03 g, 26.4 mmol) were successively added thereto, and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added a solution of sodium carbonate (3.73 g, 35.2 mmol) in water (40 mL), and the mixture was warmed to 57° C., and stirred for 5 hr. The mixture was concentrated under reduced pressure to adjust the volume of the residue to 45 mL. Ethyl acetate (50 mL) was added thereto at 45° C., and the mixture was stirred. The reaction mixture was stirred with cooling to room temperature and then cooling to 5° C. The crystals were collected by filtration, and washed with ethyl acetate (40 mL) cooled to 5° C. The obtained wet crystals were dried under reduced pressure to give crude 6-((7S)-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide (5.3 g, 17.3 mmol). yield 98%.

1. temperaturethe mixture was warmed to 57° C.
2. stirringstirred for 5 hr
3. concentrationThe mixture was concentrated under reduced pressure
4. additionEthyl acetate (50 mL) was added
5. stirringat 45° C., and the mixture was stirred
6. stirringThe reaction mixture was stirred
7. temperaturewith cooling to room temperature
8. temperaturecooling to 5° C
9. filtrationThe crystals were collected by filtration
10. washwashed with ethyl acetate (40 mL)
11. temperaturecooled to 5° C
12. customThe obtained wet crystals were dried under reduced pressure

ORD record

ord-2c39c3253edc4a8281a70a5a209cc385

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09278938B2