反应详情

温度

-10 °C

To a stirred mixture of DMF (15 mL) and NaH (60% in mineral oil, 75 mg, 1.9 mmol) at −10° C. under argon was added 4-bromo-5-methoxy-2-nitroaniline (490 mg, 2.2 mmol) in one portion. The mixture was stirred for 5 min at −10° C. A solution of 6-(chloromethyl)-2-(methylthio)benzo[d]thiazole from Example 36 (500 mg, 2.2 mmol) in DMF (5 mL) was added dropwise. After stirring at −10° C. for 1 h, the mixture was allowed to warm slowly to rt. The mixture was stirred at rt for 58 h and then partitioned between EtOAc (150 mL) and 1 M aq Na2CO3 (50 mL). The EtOAc layer was separated and washed with water (50 mL) and brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with a gradient of 100% hexanes to 100% EtOAc to afford 4-bromo-5-methoxy-N-((2-(methylthio)benzo[d]thiazol-6-yl)methyl)-2-nitroaniline (239 mg, 25%) as an orange solid. 1H NMR (300 MHz, DMSO-d6) δ 9.02 (t, J=5.8 Hz, 1H), 8.23 (s, 1H), 8.06 (s, 1H), 7.83 (d, J=8.5 Hz, 1H), 7.53 (d, J=8.3 Hz, 1H), 6.40 (s, 1H), 4.80 (d, J=5.8 Hz, 2H), 3.77 (s, 3H), 2.78 (s, 3H). LCMS (ESI) m/z 440 and 442 (M+H)+.

1. stirringAfter stirring at −10° C. for 1 h
2. temperatureto warm slowly to rt
3. stirringThe mixture was stirred at rt for 58 h
4. custompartitioned between EtOAc (150 mL) and 1 M aq Na2CO3 (50 mL)
5. customThe EtOAc layer was separated
6. washwashed with water (50 mL) and brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationthe filtrate was concentrated under reduced pressure
10. customThe residue was purified by silica gel flash chromatography
11. washeluting with a gradient of 100% hexanes to 100% EtOAc