3-Aminopyridine → 1-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

Participants

Reaction Steps

DIPEA (135.9 mg, 1.05 mmol) was added to a stirred solution of [(1-pyridin-3-yl-1H-[1,2,3]triazole-4-carbonyl)-amino]-acetic acid (prepared by the method used for the synthesis of Intermediate 64, starting from 3-aminopyridine, and subsequently, application of Step 3 of the General Scheme) (65 mg, 0.26 mmol) in DMF (2 mL) followed by HOBt (39 mg, 0.29 mmol) and EDCI (101 mg, 0.52 mmol). After 2 minutes of stirring, 4-(2,5-difluoro-phenoxy)-piperidine hydrochloride (prepared by the method used for the synthesis of Intermediate 15) (65.6 mg, 0.26 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the resultant was extracted with DCM. The organic layer was collected and dried over sodium sulfate and concentrated under reduced pressure The residue obtained was purified by stirring in mixture of 30% EtOAc in hexane (10 mL), H2O (0.5 mL) and MeOH (0.5 mL) for 30 minutes. Filtered the mixture to afford 54 mg (46.5% Yield) of 1-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 443.16, 92.48%. 1H NMR (300 MHz, DMSO-d6): δ 9.45 (s, 1H), 9.2 (d, 1H), 8.75 (m, 1H), 8.5 (t, 1H), 8.4 (m, 1H), 7.7 (q, 1H), 7.32-7.2 (m, 2H), 6.7-6.4 (m, 1H), 4.8-4.7 (m, 1H), 4.25 (d, 2H), 4.0-3.8 (m, 1H), 3.8-3.7 (m, 1H), 3.4 (m, 1H), 3.3 (m, 1H), 2.1-1.9 (m, 2H), 1.8-1.5 (m, 2H).

Provenance & Evidence