Hydrochloric Acid → HCID 86712697, compound

Participants

Reaction Steps

HOBt (0.036 g, 0.27 mmol), EDCl.HCl (0.052 g, 0.27 mmol) and DIPEA (0.18 mL, 1.0 mmol) were added to a solution of 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)-4-methylphenyl)acetic acid (A89) (0.12 g, 0.21 mmol) in dry THF (6 mL) and dry DMF (1 mL) under a nitrogen atmosphere. After 10 minutes ammonium carbonate (0.10 g, 1.0 mmol) was added in one portion and the resulting mixture stirred at room temperature for 20 hours. The volatiles were removed in vacuo and the residue dried under high vacuum. The resulting residue was taken up in dry THF (5 mL) and dry DMF (4 mL) under a nitrogen atmosphere and HOBt (0.036 g, 0.27 mmol), EDCl.HCl (0.052 g, 0.27 mmol) and DIPEA (0.18 mL, 1.0 mmol) were added. After 10 minutes ammonium carbonate (0.10 g, 1.0 mmol) was added in one portion and the resulting mixture was stirred at 25° C. for 22 hours. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (65 mL) and saturated aqueous NaHCO3 (65 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, the volatiles removed in vacuo and the residue absorbed onto silica gel and purified by column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A90 as a white solid (0.106 g, 86%); 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 7.88 (s, 1H), 7.54 (d, J=8.5 Hz, 2H), 7.18 (d, J=8.5 Hz, 2H), 7.13 (d, J=7.6 Hz, 1H), 7.08-7.01 (m, 2H), 5.78 (s, 1H), 5.47 (s, 1H), 4.39-4.15 (m, 2H), 3.66 (s, 2H), 3.04 (apparent s, 4H), 2.79 (t, J=12.2 Hz, 2H), 2.62 (tt, J=12.0, 3.3 Hz, 1H), 2.32 (s, 3H), 1.81 (d, J=12.7 Hz, 2H), 1.60 (qd, J=12.8, 4.2 Hz, 2H), 1.48 (s, 9H). LCMS-A: rt 6.63 min; m/z 598.4 [M+H]+.

Provenance & Evidence