Dimethylacetamide → N-methyl-6-[(1-tosyl-1H-imidazol-4-yl)carbonyl]-2-naphthamide

Temperature

60 °C

6-(Hydroxy(1-tosyl-1H-imidazol-4-yl)methyl)-N-methyl-2-naphthamide (8.2 g, 18.8 mmol) and manganese dioxide (14.7 g, 169.1 mmol) were added to N,N-dimethylacetamide (70 mL), and the mixture was stirred at 60° C. for 7 hr. The insoluble material was filtered off from the obtained reaction mixture at 60° C., and washed with N,N-dimethylacetamide (33 mL). The filtrate and washing were combined, and cooled to 40° C., water (49 mL) was added dropwise thereto, and the mixture was stirred at the same temperature for 0.5 hr or more, and then at room temperature for 1 hr or more to give crystals. The obtained crystals were collected by filtration, and washed with water (51 mL) to give wet crystals. The obtained wet crystals were dried under reduced pressure at an outside temperature of 50° C. to give crude crystals (6.6 g). Ethyl acetate (66 mL) were warmed to 40° C., and the crude crystals (6.6 g) were added thereto. The obtained mixture was warmed to 50° C., and stirred for 0.5 hr or more, and 13 mL of the solvent was evaporated under reduced pressure. The obtained residue was allowed to cool to room temperature, diisopropyl ether (53 mL) was added dropwise thereto at the same temperature, and the mixture was stirred to give crystals. The obtained crystals were collected by filtration, and washed with a mixed solvent (20 mL) of diisopropyl ether/ethyl acetate (1:1, volume ratio) to give wet crystals. The obtained wet crystals were dried under reduced pressure at an outside temperature of 50° C. to give N-methyl-6-[(1-tosyl-1H-imidazol-4-yl)carbonyl]-2-naphthamide (6.5 g, 15.0 mmol). yield 79%.

1. filtrationThe insoluble material was filtered off from the obtained reaction mixture at 60° C.
2. washwashed with N,N-dimethylacetamide (33 mL)
3. washThe filtrate and washing
4. temperaturecooled to 40° C.
5. additionwater (49 mL) was added dropwise
6. stirringthe mixture was stirred at the same temperature for 0.5 hr or more
7. customat room temperature for 1 hr or more to give crystals
8. filtrationThe obtained crystals were collected by filtration
9. washwashed with water (51 mL)
10. customto give wet crystals
11. customThe obtained wet crystals were dried under reduced pressure at an outside temperature of 50° C.
12. customto give crude crystals (6.6 g)
13. temperatureThe obtained mixture was warmed to 50° C.
14. stirringstirred for 0.5 hr or more
15. custom13 mL of the solvent was evaporated under reduced pressure
16. temperatureto cool to room temperature
17. additiondiisopropyl ether (53 mL) was added dropwise
18. stirringat the same temperature, and the mixture was stirred
19. customto give crystals
20. filtrationThe obtained crystals were collected by filtration
21. washwashed with a mixed solvent (20 mL) of diisopropyl ether/ethyl acetate (1:1, volume ratio)
22. customto give wet crystals
23. customThe obtained wet crystals were dried under reduced pressure at an outside temperature of 50° C.

ORD record

ord-22ee88f860dc4010bf41bda54485c0a9

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09278938B2