反应详情

温度

78 °C

To a 40 ml vial containing pyridine-2-carboxylic acid [3-(2-chloro-acetylamino) adamantan-1-yl]-amide (1.69 g, 4.85 mmol, from step 2) and thiourea (0.56 g, 7.4 mmol), was added ethanol (20.0 mL), and acetic acid (4.0 mL). The mixture was stirred at 78° C. overnight. The reaction solution was cooled to rt, poured into water (100 mL), and the pH of the solution was adjusted to 10-13 using 10 N aq. NaOH. The mixture vas transferred into a separation funnel, extracted with DCM (3×150 mL). Combined organic layer was washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure to afford 1.35 g (95.4%) of crude title compound, pyridine-2-carboxylic acid (3-amino-adamantan-1-yl)-amide, as an oil, which became a colorless solid upon standing at room temperature. LC-MS (Gradient: acetonitrile in water, 10-85%, in 1.7 minutes with a cycle time of 2 min. Flow rate: 5.0 mL/min. Mobile phase additive: 30 mM of ammonium formate. Column: Inertsil® C8, 50×4.6 mm, 3 μm particle size (GL Sciences, Tokyo, Japan)): Retention time: 0.63 min; purity (UV254): 93%; ESI-MS m/z: 272 (M+H)+. It was used in the next step, amidation, without further purification.

1. temperatureThe reaction solution was cooled to rt
2. customThe mixture vas transferred into a separation funnel
3. extractionextracted with DCM (3×150 mL)
4. washCombined organic layer was washed with water and brine
5. dry with materialdried over Na2SO4
6. concentrationconcentrated under reduced pressure