Triethylamine → 4-(4-Chloro-3-methyl-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylic acid isopropyl ester

Participants

Reaction Steps

Triethylamine (0.33 mL, 2.4 mmol) was added to a stirred mixture of 4-hydrazino-piperidine-1-carboxylic acid isopropyl ester hydrochloride (Intermediate 10; 188 mg, 0.8 mmol) and 1-(4,6-dichloro-pyrimidin-5-yl)-ethanone (Intermediate 17; 150 mg, 0.8 mmol) in toluene (5 mL) at room temperature under nitrogen and the resulting mixture was heated to reflux for 8 hours. The solvent was removed in vacuo and the crude reaction mixture was purified on a flash silica column (30 mm×4″) eluting with 10-33% ethyl acetate/hexanes to give 4-(4-chloro-3-methyl-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid isopropyl ester (90 mg, 33%). 1H NMR (300 MHz, DMSO-d6) δ 1.19 (d, 6H, J=6.3 Hz), 1.86-1.99 (m, 4H), 2.63 (s, 3H), 2.94-3.10 (m, 2H), 4.04-4.15 (m, 1H), 4.74-4.82 (m, 1H), 4.91-4.98 (m, 1H), 8.77 (s, 1H).

Provenance & Evidence