反应详情

温度

100 °C

To a degassed solution of N-(5-bromo-6-methyl-pyridin-2-yl)-acetamide (4.16 g, 18.18 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (4.37 g, 21.81 mmol, 1.2 equiv; commercially available) in toluene (40 mL) was added KOtert-Bu (5.10 g, 45.44 mmol, 2.5 equiv), dicyclohexyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphane (0.17 g, 0.36 mmol, 0.02 equiv; X-Phos ligand [CAS RN 564483-18-7]; commercially available from Strem Chemicals, USA) and tris(dibenzylideneacetone)dipalladium(0) (1.51 g, 1.45 mmol, 0.08 equiv). The reaction mixture was stirred under nitrogen at 100° C. for 16 h, cooled to rt, filtered and the filtrate concentrated by evaporation under reduced pressure. The crude material was purified with silica column chromatography eluting with a gradient of dichloromethane/methanol (10:0→9:1) and then recrystallized from diethylether to provide 0.38 g (6%) of the title compound in 90% purity according to 1H NMR. 1H NMR (250 MHz, DMSO): δ 1.31 (d, J=9.2 Hz, 2H), 1.40 (s, 9H), 1.86 (d, J=11.4 Hz, 2H), 1.99 (s, 3H), 2.24 (s, 3H), 2.86 (br s, 2H), 3.41 (br s, 1H), 3.92 (d, J=14.0 Hz, 2H), 4.51 (d, J=8.1 Hz, 1H), 7.00 (d, J=8.8 Hz, 1H), 7.69 (d, J=8.7 Hz, 1H), 9.98 (s, 1H). MS (ESI): 349.3 [M+H]+.

1. temperaturecooled to rt
2. filtrationfiltered
3. concentrationthe filtrate concentrated by evaporation under reduced pressure
4. customThe crude material was purified with silica column chromatography
5. washeluting with a gradient of dichloromethane/methanol (10:0→9:1)
6. customrecrystallized from diethylether