反应详情

6-Chloro-N5-(1-cyanocyclopropyl)-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide (0.14 g, 0.26 mmol) was dissolved under argon at 0° C. in N,N-dimethylformamide (1 ml). Sodium hydride (60%; 0.079 g, 1.97 mmol) was added and the mixture was stirred while cooling with ice for 1.5 h. Subsequently, propargyl bromide (0.04 mg, 0.26 mmol) was added dropwise. The reaction mixture was thawed while stirring within 16 h. Water and ethyl acetate were added and the phases were separated. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulphate, and the solvent was removed under reduced pressure. The residue is purified by means of preparative HPLC (Kromasil100, C18 250×20; eluent: acetonitrile in water, gradient: 10-100%) to obtain 0.075 g (50% of theory) of 6-chloro-N5-(1-cyanocyclopropyl)-1-(prop-2-yn-1-yl)-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide.

1. temperaturewhile cooling with ice for 1.5 h
2. stirringwhile stirring within 16 h
3. customthe phases were separated
4. washThe organic phase was washed with saturated sodium chloride solution
5. dry with materialdried over magnesium sulphate
6. customthe solvent was removed under reduced pressure
7. customThe residue is purified by means of preparative HPLC (Kromasil100, C18 250×20