反应详情

A 100-mL round-bottom flask was charged with N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (INTERMEDIATE A, 1.478 g, 5.88 mmol) and THF (10 mL) to give a clear, light-yellow solution. The flask was cooled in a dry ice-acetone bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (5.88 mL, 5.88 mmol) was added dropwise over 2 min. The cooling bath was removed for 5 minutes, then re-cooled for 5 min. A solution of 4-fluoro-3-nitrobenzene-1-sulfonyl chloride (1.281 g, 5.35 mmol) in THF (3 mL with a 1 mL flask/syringe wash) was added dropwise over 2 minutes. The cooling bath was removed and the reaction was warmed to room temperature. The mixture was diluted with water and extracted with EtOAc. The organic extract was washed with brine, dried over sodium sulfate, filtered, and concentrated. The material was concentrated from EtOAc (2×), then taken up in EtOAc, sonicated for 1 min, and filtered through a membrane filter. The resulting solid was transferred to a sonication vial, then put under high vacuum at 60° C. for 10 min to give N-(2,4-dimethoxybenzyl)-4-fluoro-3-nitro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (INTERMEDIATE S) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ=8.24 (s, 1 H), 8.18 (dd, J=2.4, 6.7 Hz, 1 H), 7.99 (ddd, J=2.4, 3.9, 8.8 Hz, 1H), 7.33-7.28 (m, 1 H), 7.09 (d, J=8.4 Hz, 1 H), 6.32 (dd, J=2.3, 8.4 Hz, 1 H), 6.21 (d, J=2.4 Hz, 1 H), 5.37 (s, 2 H), 3.76 (s, 3 H), 3.63 (s, 3 H). m/z (ESI) 477.0 (M+Na)+.

1. customto give a clear, light-yellow solution
2. temperatureThe flask was cooled in a dry ice-acetone bath for 10 min
3. customThe cooling bath was removed for 5 minutes
4. temperaturere-cooled for 5 min
5. customThe cooling bath was removed
6. additionThe mixture was diluted with water
7. extractionextracted with EtOAc
8. extractionThe organic extract
9. washwas washed with brine
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. concentrationThe material was concentrated from EtOAc (2×)
14. customsonicated for 1 min
15. filtrationfiltered through a membrane
16. filtrationfilter