Hydrochloric Acid → HCID 12003961, compound

Participants

Reaction Steps

The mixture of 3-(4-{3-[(R)-[(2S,5R)-4-(3-Fluoro-benzyl)-2,5-dimethyl-piperazin-1-yl]-(3-hydroxy-phenyl)-methyl]-benzoyl}-[1,4]diazepan-1-yl)-propionic acid ethyl ester (800 mg, Example 14), THF (10 mL) and 1 N NaOH solution (6 mL) was stirred at room temperature for overnight. The reaction solution was neutralized by the addition of 1 N HCl solution (6 mL). The mixture was dried under rotary evaporator. For the complete removal of water, CH3OH (25 mL) was added to the flask containing the desired product and the resulting solution was dried by rotary evaporator. The process of adding CH3OH and drying CH3OH was repeated one more time. Ethanol (20 mL) was added to the residual remained in the flask. Solid (NaCl) was seen in the ethanol solution. The mixture was filtered thru a fritted filter. The solid was resined by ethanol (15 mL). The filtrate was concentrated to give crude product, which was purified by reverse phase C-18 column chromatography conducted on CombiFlash™ Sq 16× (gradient: 100% water to 100% methanol) to give 3-(4-{3-[(R)-[(2S,5R)-4-(3-fluoro-benzyl)-2,5-dimethyl-piperazin-1-yl]-(3-hydroxy-phenyl)-methyl]-benzoyl}-[1,4]diazepan-1-yl)-propionic acid (320 mg; 42%). 1H NMR (300 MHz, CD3OD) δ 7.61 (m, 1H), 7.50-7.39 (m, 2H), 7.32 (m, 2H), 7.20-7.08 (m, 3H), 6.98 (m, 1H), 6.73 (m, 3H), 5.16 (s, 1H), 3.99-3.92 (m, 2H), 3.60 (bs, 1H), 3.50 (m, 2H), 3.35 (m, 2H), 3.23 (m, 3H), 3.08 (m, 1H), 2.99 (m, 1H), 2.75-2.66 (m, 4H), 2.54 (m, 1H), 2.46 (m, 1H), 2.17-1.99 (m, 4H), 1.13 (m, 6H).

Provenance & Evidence