Nitrogen → 4-[4-(6-Aminopyridin-3-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

Into a well stirred suspension of 2-amino-5-bromopyridine (14.6 g, 84.8 mmol), 4-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1H-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butylester (40.0 g, 106 mmol) and Cs2CO3 (55.1 g, 170 mmol) in dioxane (700 mL)/water (140 mL) was bubbled N2 gas for 15 min at ambient temperature. Pd(PPh3)4 (4.8 g, 4.2 mmol) was then added to the solution followed by N2 gas bubbling for another 10 min. The reaction mixture was then heated at 100° C. for 3 h. The cooled reaction mixture was concentrated under reduced pressure to yield an off-white residue. It was stirred with water/DCM (100 mL each) for 5 min, and the organic layer was separated. The aqueous layer was extracted with DCM (3×100 mL). The combined organic layers were washed with water (50 mL) followed by brine (50 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to yield a light yellowish residue. It was triturated with 1:1 EtOAc:Hexane (100 mL) with ice cooling for 10 min. Off-white crystals separated out which were filtered and dried in vacuo to give the title compound as white solid. 1H NMR (300 MHz, CDCl3): δ=1.49 (s, 9H), 1.89-2.03 (m, 2H), 2.12-2.22 (m, 2H), 2.91 (m, 2H), 4.23-4.28 (m, 3H), 4.48 (s, broad, 2H), 6.53 (d, J=8.4 Hz, 1H), 7.24-7.33 (d, J=8.4 Hz, 1H), 7.67 (s, 1H), 7.90 (d, 1H, J=2.1 Hz), 8.25 (d, 1H, J=2.1 Hz).

Provenance & Evidence