Hydrochloric Acid → HCID 86712704, compound

Participants

Reaction Steps

DIPEA (0.16 mL, 0.92 mmol) was added to a mixture of 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)-6-(trifluoromethyl)phenyl)acetic acid (A96) (0.104 g, 0.160 mmol), HOBt (0.037 g, 0.27 mmol), and EDCl.HCl (0.056 g, 0.29 mmol) in DMF (5.0 mL) under a nitrogen atmosphere. After 15 minutes ammonium carbonate (0.077 g, 0.80 mmol) was added and stirring continued at room temperature for 24 hours. Additional HOBt (0.072 g, 0.53 mmol), EDCl.HCl (0.056 g, 0.29 mmol) and DIPEA (0.16 mL, 0.92 mmol) were added, then and after 15 minutes ammonium carbonate (0.121 g, 1.26 mmol) was also added and the resulting mixture stirred at room temperature for 16 hours. The resulting mixture was diluted with water (20 mL) then extracted with EtOAc (3×20 mL). The combined organic extracts were concentrated under reduced pressure and the residue purified using silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.) to give the title compound A97 (75 mg, 72%); 1H NMR (400 MHz, d6-DMSO) δ 10.16 (s, 1H), 8.66 (s, 1H), 7.64 (d, J=8.6 Hz, 2H), 7.57 (d, J=7.9 Hz, 1H), 7.51 (d, J=7.4 Hz, 1H), 7.47 (s, 1H), 7.41 (dd, J=7.7, 7.7 Hz, 1H), 7.19 (d, J=8.6 Hz, 2H), 6.96 (s, 1H), 4.07 (m, 2H), 3.74 (s, 2H), 3.09 (m, 4H), 2.79 (m, 2H), 2.62 (m, 1H), 1.74 (m, 2H), 1.49 (m, 2H), 1.42 (s, 9H). LCMS-A: rt 6.63 min; m/z 652.3 [M+H]+.

Provenance & Evidence