N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → 3-fluoro-N-(4-methoxybenzyl)-4-nitro-N-(thiazol-2-yl)benzenesulfonamide

Temperature

25 °C

To a solution of N-(4-methoxybenzyl)thiazol-2-amine (1 g, 4.577 mmol) in THF (30 mL) was added LiHMDS (1.58 g, 9.09 mmol, Aldrich) at −78° C. and the reaction mixture was stirred at 25° C. for 15 min. Afterward, 3-fluoro-4-nitrobenzene-1-sulfonyl chloride (2.17 g, 9.09 mmol) dissolved in THF was added to the above mixture at −78° C. and reaction mixture was stirred at 25° C. for 1 h. The reaction mixture was cooled to 0° C. and quenched with ice water (70 mL). The organic compound was extracted with EtOAc, washed with water, dried over sodium sulfate and concentrated to get the crude material which was purified by silica gel column chromatography using a gradient of 0-40% EtOAc in hexanes as the eluent to afford 1.1 g of 3-fluoro-N-(4-methoxybenzyl)-4-nitro-N-(thiazol-2-yl)benzenesulfonamide as light yellow solid in 57.8% yield. 1H-NMR (400 MHz, DMSO): δ 8.12 (t, J=18.8 Hz, 1H), 8.09-8.07 (m, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.49-7.53 (dd, 2H), 7.22-7.32 (m, 2H), 6.88-6.98 (m, 2H), 5.07 (s, 2H), 3.71 (s, 3H).

1. additionwas added to the above mixture at −78° C.
2. customreaction mixture
3. stirringwas stirred at 25° C. for 1 h
4. temperatureThe reaction mixture was cooled to 0° C.
5. customquenched with ice water (70 mL)
6. extractionThe organic compound was extracted with EtOAc
7. washwashed with water
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated
10. customto get the crude material which
11. customwas purified by silica gel column chromatography

ORD record

ord-5449080d783f495bb2ebfe03a673b77e

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346798B2