1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Butyl 4-((3-fluoro-4-(2-(4-methylpyridin-2-ylamino)thiazol-5-ylthio)picolinamido)methyl)-4-phenylpiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Tert-butyl 4-(aminomethyl)-4-phenylpiperidine-1-carboxylate (0.385 g, 1.325 mmol, 1.2 eq) was dissolved in NMP (10 mL) and to this solution was added 3-fluoro-4-(2-(pyridin-2-ylamino)thiazol-5-ylthio)picolinic acid (0.400 g, 1.104 mmol), EDAC (0.317 g, 1.656 mmol, 1.5 eq), HOBt (0.149 g, 1.104 mmol, 1 eq) and diisopropylethylamine (0.983 mL, 5.52 mmol, 5 eq). The resulting mixture was stirred at 23° C. for 2 days. The mixture was then diluted with 10% water/90% acetonitrile/0.05% TFA, purified on preparative HPLC (ammonium acetate/water/acetonitrile) and freeze dried to give the title compound (0.270 g, 39%). 1H NMR (400 MHz, DMSO-d6) δ ppm: 1.38 (9H, s), 1.75 (2H, ddd, J=13.5, 10.2, 3.3 Hz), 2.04-2.15 (2H, m), 2.31 (3H, s), 2.91 (2H, br s), 3.42 (2H, d, J=6.32 Hz), 3.59-3.70 (2H, m), 6.86 (1H, t, J=5.3 Hz), 6.91 (1H, s), 7.03 (1H, t, J=5.31 Hz), 7.25 (1H, t, J=7.07 Hz), 7.34-7.45 (4H, m), 7.81 (1H, s), 8.16 (1H, t, J=4.55 Hz), 8.21 (1H, d, J=5.05 Hz), 8.25 (1H, d, J=6.44 Hz), 11.78 (1H, s). LC/MS (M+H)+: 635. HPLC ret. time (Condition C): 7.033 min.

Provenance & Evidence