1-Hydroxybenzotriazole → HCID 50988203, compound

To 3-aminosulfonylbenzoic acid (4.0 g), N,N-dimethylformamide (53 ml), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.8 g), 1-hydroxybenzotriazole (2.7 g), N,O-dimethylhydroxylamine hydrochloride (1.9 g), and triethylamine (2.8 ml) were added under ice cooling and the mixture was stirred at room temperature for 12 hours. A potassium hydrogensulfate aqueous solution and ethyl acetate were added to the reaction solution and the mixture was separated. The aqueous layer was extracted with ethyl acetate. The combined organic layer was successively washed with distilled water, saturated sodium hydrogencarbonate aqueous solution, and saturated saline, dried over with anhydrous sodium sulfate, then concentrated. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2). To the obtained N-methoxy-N-methyl-3-aminosulfonylbenzamide (1.8 g), tetrahydrofuran (36 ml) and ethyl magnesium bromide (0.89M tetrahydrofuran solution, 41 ml) were added under ice cooling, the mixture was stirred at room temperature for 3 hours, then saturated ammonium chloride aqueous solution and ethyl acetate were added to reaction solution, the mixture was separated, then organic layer was successively washed with saturated saline, dried over with anhydrous sodium sulfate, then concentrated. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1). To the obtained 3-propionylbenzenesulfonamide (0.97 g), ethanol (2.5 ml), sodium acetate (0.56 g), and hydroxylamine hydrochloride (0.35 g) were added and the mixture was stirred at 90° C. for 3 hours. Ethyl acetate and water were added to the reaction solution, the mixture was separated, then the organic layer was successively washed with saturated saline, dried over with anhydrous sodium sulfate, then concentrated. The obtained 3-(N-hydroxypropanimidoyl) benzenesulfonamide was used instead of the starting material compound of Reference Example 109, that is, 1-(4-aminophenyl)propan-1-on oxime, for the similar procedure as with Reference Example 109 to obtain the title compound.

1. customthe mixture was separated
2. extractionThe aqueous layer was extracted with ethyl acetate
3. washThe combined organic layer was successively washed with distilled water, saturated sodium hydrogencarbonate aqueous solution, and saturated saline
4. dry with materialdried over with anhydrous sodium sulfate
5. concentrationconcentrated
6. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/2)
7. additionTo the obtained N-methoxy-N-methyl-3-aminosulfonylbenzamide (1.8 g), tetrahydrofuran (36 ml) and ethyl magnesium bromide (0.89M tetrahydrofuran solution, 41 ml) were added under ice cooling
8. stirringthe mixture was stirred at room temperature for 3 hours
9. additionsaturated ammonium chloride aqueous solution and ethyl acetate were added to reaction solution
10. customthe mixture was separated
11. washorganic layer was successively washed with saturated saline
12. dry with materialdried over with anhydrous sodium sulfate
13. concentrationconcentrated
14. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=1/1)
15. additionTo the obtained 3-propionylbenzenesulfonamide (0.97 g), ethanol (2.5 ml), sodium acetate (0.56 g), and hydroxylamine hydrochloride (0.35 g) were added
16. stirringthe mixture was stirred at 90° C. for 3 hours
17. additionEthyl acetate and water were added to the reaction solution
18. customthe mixture was separated
19. washthe organic layer was successively washed with saturated saline
20. dry with materialdried over with anhydrous sodium sulfate
21. concentrationconcentrated

ORD record

ord-7b65b1d724034f56b83306fde5c2a262

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07888348B2