Reacción #363228

Ecuación de reacción

6-carboxy-1-(2-chlorobenzyl)-2-methylbenzimidazole

4-methoxybenzenesulfonamide

diazabicycloundecene

→

1-(2-chlorobenzyl)-6-(4-methoxybenzenesulfonylcarbamoyl)-2-methylbenzimidazole

Rendimiento 72.0%

Disolventes

N,N-dimethylformamide

N,N-dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGthe mixed solution was stirred at 100° C. for 67 hours
2. 2
   TemperaturaThe reaction solution was cooled
3. 3
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
4. 4
   workup.ADDITIONwater and chloroform were added to the residue, and 10% hydrochloric acid
5. 5
   workup.ADDITIONwas added
6. 6
   Temperaturawhile being cooled until the aqueous layer
7. 7
   ExtracciónThe resulting mixture was extracted twice with chloroform
8. 8
   LavadoThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate
9. 9
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
10. 10
    OtroThe residue was purified through silica-gel column chromatography (eluent
11. 11
    workup.ADDITIONa mixture of chloroform and methanol at a ratio of 100:2 to 100:10)
12. 12
    ConcentraciónThe resulting product was concentrated
13. 13
    Otrowas crystallized from a mixed solution of ethyl acetate and diethyl ether
14. 14
    OtroThe crystals were separated through filtration
15. 15
    Otrowere dried

Procedimiento

N,N′-carbodiimidazole (0.431 g) was added at a time to a solution of 0.400 g of 6-carboxy-1-(2-chlorobenzyl)-2-methylbenzimidazole in 15 ml of N,N-dimethylformamide, and the mixture was stirred at room temperature for 1 hour. Subsequently, a solution of 0.498 g of 4-methoxybenzenesulfonamide and 0.405 g of diazabicycloundecene in 5 ml of N,N-dimethylformamide was added thereto, and the mixed solution was stirred at 100° C. for 67 hours. The reaction solution was cooled, and the solvent was distilled off under reduced pressure. water and chloroform were added to the residue, and 10% hydrochloric acid was added thereto while being cooled until the aqueous layer was acidified. The resulting mixture was extracted twice with chloroform. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, and the solvent was distilled off under reduced pressure. The residue was purified through silica-gel column chromatography (eluent: a mixture of chloroform and methanol at a ratio of 100:2 to 100:10). The resulting product was concentrated, and was crystallized from a mixed solution of ethyl acetate and diethyl ether. The crystals were separated through filtration, and were dried to give 0.450 g of 1-(2-chlorobenzyl)-6-(4-methoxybenzenesulfonylcarbamoyl)-2-methylbenzimidazole (217).

Fuente