Triethylamine → 5-Chloro-1-[5-chloro-2-(dimethylsulfamoyl)benzyl]-2-imino-1,2-dihydropyridine-3-carboxamide hydrochloride

Temperature

50 °C

(Step 3) To a suspension of 2-cyano-2-(3,4-dichloro-5-oxo-2,5-dihydrofuran-2-yl)acetamide (0.50 g) in methanol (10 ml) was added a solution of 2-(aminomethyl)-4-chloro-N,N-dimethylbenzenesulfonamide hydrochloride obtained in Step 2 (0.85 g) and triethylamine (0.58 ml) in methanol (5 ml) at room temperature, and the mixture was stirred overnight at 50° C. The reaction solvent was evaporated under reduced pressure, acetic acid (5 ml) was added, and the mixture was stirred at 50° C. for 2 hr. The solvent was evaporated under reduced pressure, the residue was extracted with 1N hydrochloric acid, and the extract was washed with ethyl acetate. The aqueous layer was basified with 1N aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=7:3→1:0). The obtained residue was dissolved in methanol, and 4N hydrogen chloride-ethyl acetate solution (1 ml) was added. The mixture was crystallized from methanol-ethyl acetate. The precipitated crystals were collected by filtration, and recrystallized from methanol-ethyl acetate to give the title compound (0.43 g).

1. customThe reaction solvent was evaporated under reduced pressure, acetic acid (5 ml)
2. additionwas added
3. stirringthe mixture was stirred at 50° C. for 2 hr
4. customThe solvent was evaporated under reduced pressure
5. extractionthe residue was extracted with 1N hydrochloric acid
6. washthe extract was washed with ethyl acetate
7. extractionthe mixture was extracted with ethyl acetate
8. dry with materialThe organic layer was dried over sodium sulfate
9. customThe solvent was evaporated under reduced pressure
10. customThe residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=7:3→1:0)
11. dissolutionThe obtained residue was dissolved in methanol
12. addition4N hydrogen chloride-ethyl acetate solution (1 ml) was added
13. customThe mixture was crystallized from methanol-ethyl acetate
14. filtrationThe precipitated crystals were collected by filtration
15. customrecrystallized from methanol-ethyl acetate

ORD record

ord-580abdc7cb364ef293fbbbdde7312f08

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08481569B2