反应详情

Isothiocyanatomethane (0.055 g, 0.746 mmol) in N,N-dimethylformamide (1.0 mL) was added dropwise slowly to a stirred solution of 5-bromo-3-methylbenzene-1,2-diamine (0.150 g, 0.746 mmol) in N,N-dimethylformamide (1.5 mL) at 0° C. The cold bath was removed, the reaction mixture was capped and stirred at room temperature for 48 h. N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (0.157 g, 0.821 mmol) was added and the reaction mixture capped and heated at 40° C. overnight. The resulting mixture was diluted with methanol, filtered and purified using reverse-phase preparatory HPLC (10-50% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min). Fractions containing the desired product were combined and most of the solvent removed under reduced pressure. Acetonitrile was added and the resulting mixture loaded on a Strata ion exchange column. The column was washed successively with water, acetonitrile, methanol and 5% ammonium hydroxide in methanol. The product eluted with the 5% ammonium hydroxide in methanol and was concentrated under reduced pressure and dried under high vacuum to give the desired product (0.128 g, 0.53 mmol, 72% yield) as a slightly yellow waxy solid. MS (ESI) m/z 240 [M]+, 242 [M+2]+.

1. customThe cold bath was removed
2. customthe reaction mixture was capped
3. customthe reaction mixture capped
4. temperatureheated at 40° C. overnight
5. filtrationfiltered
6. custompurified
7. customreverse-phase preparatory HPLC (10-50% acetonitrile+0.1% TFA in H2O+0.1% TFA, over 30 min)
8. additionFractions containing the desired product
9. customremoved under reduced pressure
10. additionAcetonitrile was added
11. washThe column was washed successively with water, acetonitrile, methanol and 5% ammonium hydroxide in methanol
12. washThe product eluted with the 5% ammonium hydroxide in methanol
13. concentrationwas concentrated under reduced pressure
14. customdried under high vacuum