2-Acetylamino-5-bromo-3-methylpyridine → HCID 67195457, compound

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of N-(5-bromo-3-methyl-pyridin-2-yl)-acetamide (4.92 g, 21.48 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (5.16 g, 25.77 mmol, 1.2 equiv; commercially available) in toluene (40 mL) was added KOtert-Bu (6.03 g, 53.69 mmol, 2.5 equiv), dicyclohexyl-(2′,4′,6′-triisopropyl-biphenyl-2-yl)-phosphane (0.21 g, 0.43 mmol, 0.02 equiv; X-Phos ligand [CAS RN 564483-18-7]; commercially available from Strem Chemicals, USA) and tris(dibenzylideneacetone)dipalladium(0) (1.78 g, 1.72 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 ethyl acetate/triethylamine (10:0→4:1) and then recrystallized from ethyl acetate/heptane to provide 2.96 g (45%) of the title compound in 70% purity according to 1H NMR. 1H NMR (250 MHz, DMSO): δ 1.03-1.28 (m, 2H), 1.39 (s, 9H), 1.82 (dd, J=12.3 Hz, J=3.9 Hz, 2H), 1.98 (s, 3H), 2.72-2.98 (m, 2H), 3.11-3.29 (m, 1H), 3.84 (d, J=13.4 Hz, 2H), 4.52 (d, J=8.7 Hz, 1H), 5.60 (br s, 2H), 6.73 (d, J=2.3 Hz, 1H), 7.29 (d, J=2.7 Hz, 1H). MS (ESI): 307.2 [M+H]+.

Provenance & Evidence