Hydrochloric Acid → HCID 12003966, compound

Participants

Reaction Steps

To the compound of Example 9 (335 mg) in THF (4 mL) was added 1N NaOH solution (3.0 mL). The reaction was stirred at room temperature for overnight. The reaction solution was neutralized by the addition of 1 N HCl solution (3.0 mL). The mixture was put under rotary evaporator for the removal of THF. The remaining water layer was diluted by water (5 mL). The water layer was extracted by n-butanol (6 mL×3). The combined n-butanol layer was washed by water (5 mL×2) and concentrated to give crude product (225 mg), which was purified by silica gel chromatography conducted on CombiFlash™ Sq 16× (gradient: 100% CH2Cl2 to 30% MeOH in CH2Cl2) to give 5-(4-{3-[(R)-((2S,5R)-4-allyl-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-[1,4]diazepan-1-yl)-pentanoic acid (217 mg; 68%). 1H NMR (300 MHz, DMSO-d6) δ 9.36 (bs, 1H), 8.31 (s, 1H), 7.35 (m, 3H), 7.18 (m, 1H), 7.12 (dd, 1H, J=8.0, 8.0 Hz), 6.66 (m, 3H), 5.78 (m, 1H), 5.19-5.00 (m, 3H), 3.56 (m, 2H), 3.30 (m, 2H), 3.19 (m, 1H), 2.86 (m, 1H), 2.72 (m, 2H), 2.59-2.49 (m, 7H), 2.37 (m, 1H), 2.20 (m, 2H), 2.07 (m, 1H), 1.83 (m, 2H), 1.65 (m, 1H), 1.50-1.35 (m, 4H), 1.07 (d, 3H, J=6.0 Hz), 0.92 (d, 3H, J=5.5 Hz).

Provenance & Evidence