反应详情

温度

75 °C

To a solution of (R)-tert-butyl 4-(cis-4-(2-chloro-5-nitropyridin-4-ylamino)cyclohexanecarbonyl)-3-methylpiperazine-1-carboxylate (0.4 g, 0.830 mmol) in toluene (8.30 mL) was added 2-(piperidin-1-yl)ethanol (0.536 g, 4.15 mmol), 18-crown-6 (0.329 g, 1.245 mmol), and cesium carbonate (0.811 g, 2.490 mmol). The reaction was purged with argon and stirred at 75° C. overnight. The mixture was diluted with EtOAc to about 50 mL total volume and washed sequentially with water (50 mL), brine (50 mL), and aqueous NH4Cl (2×50 mL). The organic layer was dried over sodium sulfate and concentrated to afford an orange residue. The residue was purified by silica gel chromatography (1-5% MeOH/DCM, 1% NH4OH) to afford (R)-tert-butyl 3-methyl-4-(cis-4-(5-nitro-2-(2-(piperidin-1-yl)ethoxy)pyridin-4-ylamino)cyclohexanecarbonyl)piperazine-1-carboxylate as a tan solid (0.33 g, 69.2% yield). MS m/z=575.4 [M+H]. Calc'd for C29H46N6O6: 574.4.

1. customThe reaction was purged with argon
2. additionThe mixture was diluted with EtOAc to about 50 mL total volume
3. washwashed sequentially with water (50 mL), brine (50 mL), and aqueous NH4Cl (2×50 mL)
4. dry with materialThe organic layer was dried over sodium sulfate
5. concentrationconcentrated
6. customto afford an orange residue
7. customThe residue was purified by silica gel chromatography (1-5% MeOH/DCM, 1% NH4OH)