Sodium Carbonate → tert-butyl 4-(4-(6-amino-5-bromopyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a well stirred solution of 4-[4-(6-aminopyridin-3-yl)-pyrazol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (24.4 g, 71.1 mmol) in DCM (800 mL) was added solid Na2CO3 (11.2 g, 107 mmol), and the mixture was cooled to 0° C. A solution of bromine (3.6 mL, 71 mmol) in DCM (200 mL) was added dropwise during 30 min, and the reaction mixture was stirred for further 5 h at ambient temperature. The reaction mixture was then cooled to 10° C., and a cold solution of 10% sodium thiosulfate in water (100 mL) followed by saturated sodium bicarbonate solution (100 mL) was added. After stirring for 10 min, the organic layer was separated, washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to yield a brown solid. It was triturated twice with tert-butyl methyl ether (100 mL) at 40-45° C., filtered, and dried in vacuo to yield the title compound as white solid. 1H NMR (300 MHz, CDCl3): δ=1.48 (s, 9H), 1.92-1.96 (m, 2H), 2.13-2.17 (m, 2H), 2.89 (m, 2H), 4.23-4.28 (m, 3H), 4.86 (s, broad, 2H), 7.56 (s, 1H), 7.66 (s, 1H), 7.75 (d, 1H, J=2.1 Hz), 8.15 (d, 1H, J=2.1 Hz).

Provenance & Evidence