Hydrochloric Acid → HCID 20672402, compound

Participants

Reaction Steps

To a solution of DIEA (0.019 mL, 0.11 mmol) in 0.5 mL of 1,2-dichloroethane was added 4fluoro-4-(3-phenylpropyl) piperidine.HCl (21 mg, 0.08 mmol) To this solution, a solution of 2-(R)-((3-(R)-formyl)-4-(S)-phenylpyrrolidin-1-yl)-2-(cyclohexyl)acetic acid, (4-methoxy) benzyl ester (25 mg, 0.052 mmol, from EXAMPLE 33, Step E) was added. A slurry of sodium triacetoxyborohydride (35 mg, 0.17 mmol) in 0.5 mL of 1,2-dichloroethane was then added. The reaction mixture was allowed to stand at rt for 16 hours. The solvent was removed and the product was purified by preprative HPLC (column: YMC Combiprep ODS-A 20×50 mm, gradient: 10% acetonitrile/H2O w/0.1% TFA for 1.5 min then ramp to 90% acetonitrile/H2O w/0.1% TFA over 7.5 min, flow: 20 mL/min). The isolated material was stirred in 3 mL formic acid for 16 h. After removal of solvent, the residue was purified by ion exchange chromatography (0.5 grams Varian SCX resin, 100% MeOH→2.0 M NH3/MeOH) to give 13 mg (48%) of the title compound: 1H NMR (400 MHz, CD3OD) δ 1.15-1.37 (m, 4H), 1.41-1.59 (m, 5H), 1.62-1.69 (m, 5H), 1.72-1.91 (m, 5H), 2.04 (t, J=10, 1H), 2.24 (t, J=11, 1H), 2.32 (dd, J=4.5, 13, 1H), 2.46 (dd, J=10, 13 Hz, 2H), 2.58 (t, J=7.5 Hz, 2H), 2.62-2.65 (m, 1H), 2.77 (m, 1H), 3.16 (dd, J=11, 19, 1H), 3.45 (m, 2H), 3.51 (d, J=3.9, 1H), 3.58-3.64 (m, 2H), 7.12-7.16 (m, 3H), 7.22-7.29 (m, 3H), 7.33-7.37 (m, 4H); ESI-MS: 521 (M+H); HPLC A: 2.65 min.

Provenance & Evidence