反应详情

A 250-mL round-bottom flask was charged with 6-chloro-3-oxo-3,4-dihydro-2h-1-4-benzoxazine-7-sulfonyl chloride (Enamine, Kiev, Ukraine, 3.849 g, 13.64 mmol), N-(4-methoxybenzyl)thiazol-2-amine (3.61 g, 16.37 mmol), and THF (68.2 ml) to give a thick suspension. The flask was sonicated for 30 s, then cooled in a dry ice-acetone bath for 10 min. Lithium bis(trimethylsilyl)amide (1M in THF) (30.0 ml, 30.0 mmol) was added dropwise over 5 min. After another 5 min, the flask was transferred to an ice-bath. After 1 h of stirring, an additional portion of base solution (5 mL) was added. After 10 min, the mixture was diluted with saturated aq. ammonium chloride (150 mL) and water (50 mL). The mixture was extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was concentrated from DCM (2×). The resulting solid was taken up in THF (100 mL) to give a thin suspension. The flask was cooled in an ice-bath for 5 min, then borane-tetrahydrofuran complex (1M in THF) (1.173 g, 13.64 mmol). Following the addition, the cooling bath was removed. After 2 h, borane-tetrahydrofuran complex (1M in THF) from another bottle (30 mL) was added. Some bubbling was observed, and the mixture lightened. After 16 h of stirring, the mixture was quenched by the careful addition of MeOH (20 mL). After 2 h, the mixture was concentrated, then concentrated from MeOH/DCM. The residual oil was treated with MeOH, and the resulting mixture was stirred for 5 h. The sides of the flask were scraped with a spatula, and the flask was cooled in an ice-bath for 10 min. The mixture was then filtered, and the collected solid was washed with ice-cold MeOH (2×), dried under a stream of N2 (g), then dried under vacuum to give 6-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (2.3249 g, 5.14 mmol, 37.7% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ=7.41 (d, J=3.5 Hz, 1 H), 7.30-7.19 (m, 5 H), 6.85 (d, J=8.7 Hz, 2 H), 6.68 (s, 1 H), 5.15 (s, 2 H), 4.12 (t, J=4.3 Hz, 2 H), 3.71 (s, 3 H), 3.37 (d, J=2.2 Hz, 2 H); m/z (ESI) 452.2 (M+H)+.

1. customto give a thick suspension
2. customThe flask was sonicated for 30 s
3. temperaturecooled in a dry ice-acetone bath for 10 min
4. customthe flask was transferred to an ice-bath
5. waitAfter 10 min
6. extractionThe mixture was extracted with EtOAc (3×)
7. dry with materialThe combined organic extracts were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. concentrationThe residue was concentrated from DCM (2×)
11. customto give a thin suspension
12. temperatureThe flask was cooled in an ice-bath for 5 min
13. additionthe addition
14. customthe cooling bath was removed
15. waitAfter 2 h
16. additionborane-tetrahydrofuran complex (1M in THF) from another bottle (30 mL) was added
17. stirringAfter 16 h of stirring
18. customthe mixture was quenched by the careful addition of MeOH (20 mL)
19. waitAfter 2 h
20. concentrationthe mixture was concentrated
21. concentrationconcentrated from MeOH/DCM
22. additionThe residual oil was treated with MeOH
23. stirringthe resulting mixture was stirred for 5 h
24. temperaturethe flask was cooled in an ice-bath for 10 min
25. filtrationThe mixture was then filtered
26. washthe collected solid was washed with ice-cold MeOH (2×)
27. dry with materialdried under a stream of N2 (g)
28. customdried under vacuum