Hydrochloric Acid → HCID 86719438, compound

Participants

Reaction Steps

To a round bottom flask was added methyl 2-((4S,5S)-1-(4-((1-(5-methoxy-2-methylphenyl)piperidin-4-yl)oxy)phenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetate (45 mg, 0.087 mmol), 2M LiOH (0.26 mL, 0.52 mmol) and THF (1 mL). The reaction solution was stirred at rt for 1.5 h, and the solution was acidified with 1N HCl to pH<4. The mixture was extracted with EtOAc (10 mL). The organic layer was washed with water (10 mL) and brine (10 mL), and then it was dried over MgSO4, filtered and concentrated. The residue was purified by Prep-HPLC to give 2-((4S,5S)-1-(4-(1-(5-methoxy-2-methylphenyl)piperidin-4-yloxy)phenyl)-4-methyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-5-yl)acetic acid (31 mg, 0.062 mmol, 71% yield). LC-MS Anal. Calc'd for C26H30F3N3O4: 505.2. found [M+H] 506.1. 1H NMR (500 MHz, DMSO-d6) δ 7.12-7.03 (m, 3H), 6.99 (d, J=9.1 Hz, 2H), 6.59 (br. s., 1H), 6.55 (dd, J=8.3, 1.9 Hz, 1H), 4.45 (d, J=3.9 Hz, 2H), 3.72 (s, 4H), 3.39-3.33 (m, 2H), 3.05 (d, J=4.4 Hz, 2H), 2.78 (t, J=9.9 Hz, 2H), 2.66 (dd, J=16.2, 3.0 Hz, 1H), 2.18 (s, 3H), 2.05 (br. s., 2H), 1.85-1.72 (m, 2H), 1.27 (d, J=6.9 Hz, 3H). hGPR40 EC50=161 nM.

Provenance & Evidence