Water → HCID 53465112, compound

Participants

Reaction Steps

To a solution of (3R,4R)-benzyl 3-(((S)-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropyl)-2-hydroxypropanamido)methyl)-4-fluoropyrrolidine-1-carboxylate (108 mg, 0.159 mmol) in degassed ethanol (3 mL, 0.05 M solution) was added Pd/C (17.2 mg) under anhydrous N2 atmosphere. After flushed with hydrogen gas, the reaction mixture equipped with a hydrogen gas balloon was stirred at room temperature for 30 min. The reaction mixture was filtered through Celite® pad that was washed with methanol and EtOAc. The volatile organic filtrate was removed in vacuo to give the crude amine, 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 product obtained was then dissolved in acetonitrile and water (1:1 ratio) and lyophilized for 48 h. The white powdery (S)-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropyl)-N-(((3S,4R)-4-fluoropyrrolidin-3-yl)methyl)-2-hydroxypropanamide was obtained in 75% yield (66 mg, over 2 steps) as the free amine. 1H NMR (CD3Cl, 400 MHz): δ 7.87 (1H, m), 7.33-7.27 (4H, m), 7.22-7.14 (2H, m), 7.08 (1H, m), 6.08 (1H, s), 4.71-4.62 (1H, m), 4.60-4.40 (1H, m), 4.23 (2H, s), 3.95 (1H, m), 3.63 (2H, m), 3.01-2.86 (1H, m), 2.70-2.46 (2H, m), 2.14-2.06 (2H, m), 1.45 (3H, m), 1.03 (9H, s). LC/MS (uplc): MH+ 546.4, 1.00 min.

Provenance & Evidence