Hydrochloric Acid → HCID 66969614, compound

Temperature

50 °C

(Step 1) According to the method of Example 29, Steps 2 and 3, 2-(aminomethyl)-4-fluoro-N-methylbenzenesulfonamide hydrochloride was synthesized using 2-[(acetylamino)methyl]-4-fluorobenzenesulfonyl chloride, a solution of methylamine in tetrahydrofuran, and hydrochloric acid. 1H NMR (300 MHz, DMSO-d6) 8 ppm 2.46 (3H, d, J=4.9 Hz), 4.41 (2H, q, J=5.7 Hz), 7.48 (1H, td, J=8.3, 2.7 Hz), 7.58-7.68 (1H, m), 7.90-8.04 (2H, m), 8.51 (3H, br. s.). (Step 2) To a suspension of 2-cyano-2-(3,4-dichloro-5-oxo-2,5-dihydrofuran-2-yl)acetamide (0.90 g) in methanol (10 ml) was added a solution of 2-(aminomethyl)-4-fluoro-N-methylbenzenesulfonamide hydrochloride obtained in Step 1 (1.17 g) and triethylamine (1.6 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, the mixture was partitioned with ethyl acetate, and 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 (0.74 g).

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

ORD record

ord-f93cbdc899d949149e86108121599121

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08481569B2