Hydrochloric Acid → HCID 12003966, compound

HRID 2245866Notes

Reaction equation

HRID 2245866 reaction equation
C([O:3][C:4](=[O:43])[CH2:5][CH2:6][CH2:7][CH2:8][N:9]1[CH2:15][CH2:14][CH2:13][N:12]([C:16](=[O:42])[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C@@H:23]([N:31]3[CH2:36][C@@H:35]([CH3:37])[N:34]([CH2:38][CH:39]=[CH2:40])[CH2:33][C@@H:32]3[CH3:41])[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=3)[CH:18]=2)[CH2:11][CH2:10]1)C.[OH-].[Na+].Cl>C1COCC1>[CH2:38]([N:34]1[C@H:35]([CH3:37])[CH2:36][N:31]([C@@H:23]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)[C:19]2[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=2)[C:16]([N:12]2[CH2:13][CH2:14][CH2:15][N:9]([CH2:8][CH2:7][CH2:6][CH2:5][C:4]([OH:43])=[O:3])[CH2:10][CH2:11]2)=[O:42])[C@@H:32]([CH3:41])[CH2:33]1)[CH:39]=[CH2:40]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58815881HCID 58815881, compound

Product 1

HCID 12003966HCID 12003966, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  1. customThe mixture was put under rotary evaporator for the removal of THF
  2. additionThe remaining water layer was diluted by water (5 mL)
  3. extractionThe water layer was extracted by n-butanol (6 mL×3)
  4. washThe combined n-butanol layer was washed by water (5 mL×2)
  5. concentrationconcentrated
  6. customto give crude product (225 mg), which
  7. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-52caa2083da44738bd0108d0dc2fd317
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

Loading…