Sodium hydride → (S)-1-(tetrahydro-pyran-4-yl)-pyrrolidine-2-carboxylic acid (3-[1,1-dimethyl-2-(tetrahydro-pyran-2-yloxy)-ethyl]-isoxazol-5-yl)-amide

(S)-1-(Tetrahydro-pyran-4-yl)-pyrrolidine-2-carboxylic acid (0.2 g; 1.004 mmol) is dissolved in 5 mL of dimethyl formamide and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium PF6 (0.573 g, 1.506 mmol) and diethylisopropyl amine (0.626 mL, 3.514 mmol) are added. The mixture is stirred at room temperature for 30 minutes. 3-[1,1-dimethyl-2-(tetrahydro-pyran-2-yloxy)-ethyl]isoxazole-5-yl amine (0.241 g, 1.004 mmol) is dissolved in 5 mL of dimethylformamide and sodium hydride (60% in mineral oil, 0.1 g, 2.510 mmol) is added at 0° C. The above solution is added and the mixture warmed to room temperature and stirred for 1 h. The reaction is quenched with water and methanol and concentrated under reduced pressure. The crude mixture is purified by flash chromatraphy (SiO2) to afford 0.075 g of title compound as an oil. 18% yield, ESI m/z 422=MH+.

1. additionThe above solution is added
2. temperaturethe mixture warmed to room temperature
3. stirringstirred for 1 h
4. customThe reaction is quenched with water and methanol
5. concentrationconcentrated under reduced pressure
6. customThe crude mixture is purified by flash chromatraphy (SiO2)

ORDレコード

ord-d29dfb50701c4d34ae0cc9ada55e09ee

出典データセット

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08629157B2