HCID 86658514, compound → HCID 53482758, compound

Participants

Reaction Steps

To a solution of (3R,4R)-benzyl 3-(((S)—N—((R)-1-(1-benzyl-3-(2,5-difluorophenyl)-1H-1,2,4-triazol-5-yl)-2,2-dimethylpropyl)tetrahydrofuran-2-carboxamido)methyl)-4-fluoropyrrolidine-1-carboxylate (583 mg, 0.845 mmol) in degassed EtOAc (8 mL, 0.1 M solution) was added Pd/C (899 mg, 10 wt %) under anhydrous N2 atmosphere. After flushed with hydrogen gas, the reaction mixture equipped with a hydrogen gas balloon was stirred at room temperature for overnight. The reaction mixture was filtered through Celite® pad that was washed with EtOAc. The volatile organic filtrate was removed in vacuo to give the crude product, which was purified by preparative reverse phase HPLC. The combined fractions of the product were neutralized with saturated NaHCO3 solution, which was then extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The dried product was then dissolved in acetonitrile and water (1:1 ratio) and lyophilized for 48 h. The white powdery (S)—N—((R)-1-(1-benzyl-3-(2,5-difluorophenyl)-1H-1,2,4-triazol-5-yl)-2,2-dimethylpropyl)-N-(((3S,4R)-4-fluoropyrrolidin-3-yl)methyl)tetrahydrofuran-2-carboxamide was obtained in 27.9% yield (131 mg) as a free amine 1H NMR (CD3Cl, 400 MHz): δ 7.82 (1H, m), 7.53 (2H, m), 7.35-7.27 (3H, m), 7.14 (1H, m), 7.06 (1H, m), 6.14 (1H, s), 5.45 (2H, m), 4.85 (2H, m), 4.72 (1H, m), 4.21 (1H, m), 3.97 (1H, m), 3.83 (1H, m), 3.02 (1H, m), 2.80 (1H, m), 2.33-1.80 (6H, m), 1.25 (1H, s), 1.01 (1H, m), 0.99 (9H, s). LC/MS (uplc): MH+556.4, 0.99 min.

Provenance & Evidence