Hydrochloric Acid → HCID 86712732, compound

Participants

Reaction Steps

HOBt (0.051 g, 0.379 mmol), EDCl.HCl (0.081 g, 0.42 mmol) and DIPEA (0.11 mL, 0.65 mmol) were added to a solution of 2-(2-(2-(2-((1-(1-(tert-butoxycarbonyl)piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-methylpyrimidin-4-ylethyl)phenyl)acetic acid (A127) (0.068 g, 0.131 mmol) in dry DMF (5 mL) under an atmosphere of nitrogen. After 10 minutes ammonium carbonate (0.126 g, 1.31 mmol) was added in one portion and the resulting mixture stirred for 18 hours at room temperature. Additional HOBt (0.051 g, 0.38 mmol), EDCl.HCl (0.081 g, 0.42 mmol), DIPEA (0.11 mL, 0.65 mmol) and ammonium carbonate (0.126 g, 1.31 mmol) were added to the reaction mixture and the mixture stirred for 12 days at room temperature. The volatiles were removed in vacuo then the residue diluted with EtOAc (50 mL) and washed with saturated aqueous NaHCO3 (50 mL). The aqueous layer was extracted with EtOAc (2×25 mL). The combined organic layers were washed with brine (25 mL) and dried over Na2SO4. The solvent was removed in vacuo to afford a yellow oil that was purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. followed by 0-30% MeOH in EtOAc) to give the title compound A127 as an off white solid (0.044 g, 65%); 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.85 (s, 1H), 7.50 (d, J=0.5 Hz, 1H), 7.26-7.17 (m, 5H), 5.79 (s, 1H), 5.62 (s, 1H), 4.26-4.19 (m, 3H), 3.65 (s, 2H), 3.07 (dd, J=9.5, 6.2 Hz, 2H), 2.93-2.82 (m, 4H), 2.15-2.08 (m, 2H), 2.04 (s, 3H), 1.91 (qd, J=12.3, 4.3 Hz, 2H), 1.46 (s, 9H). LCMS-A: rt 5.178 min; m/z 520 [M+H]+.

Provenance & Evidence