Hydrochloric Acid → HCID 12003963, compound

HRID 2245868Notes

Reaction equation

HRID 2245868 reaction equation
C([O:3][C:4](=[O:45])[CH2:5][CH2:6][N:7]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:44])[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C@@H:21]([N:29]3[CH2:34][C@@H:33]([CH3:35])[N:32]([CH2:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[CH2:31][C@@H:30]3[CH3:43])[C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=3)[CH:16]=2)[CH2:9][CH2:8]1)C.[OH-].[Na+].Cl>C1COCC1>[CH2:36]([N:32]1[C@H:33]([CH3:35])[CH2:34][N:29]([C@@H:21]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=2)[C:17]2[CH:16]=[C:15]([CH:20]=[CH:19][CH:18]=2)[C:14]([N:10]2[CH2:11][CH2:12][CH2:13][N:7]([CH2:6][CH2:5][C:4]([OH:45])=[O:3])[CH2:8][CH2:9]2)=[O:44])[C@@H:30]([CH3:43])[CH2:31]1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 12003959HCID 12003959, compound

Product 1

HCID 12003963HCID 12003963, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the compound of Example 12 (215 mg) in THF (4 mL) was added 1N NaOH solution (1 mL). The reaction was stirred at room temperature for overnight. The reaction solution was neutralized by the addition of 1 N HCl solution (1 mL). The mixture was put under rotary evaporator for the removal of THF. The remaining water layer was diluted by water (3 mL). The water layer was extracted by n-butanol (5 mL×3). The combined n-butanol layer was washed by water (5 mL×2) and concentrated to give crude product (200 mg), which was purified by silica gel chromatography conducted on CombiFlash™ Sq 16× (gradient: 100% CH2Cl2 to 30% MeOH in CH2Cl2) to give 3-(4-{3-[(R)-((2S,5R)-4-benzyl-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl }-[1,4]diazepan-1-yl)-propionic acid (133 mg; 65%). 1H NMR (300 MHz, DMSO-d6) δ 9.36 (s, 1H), 7.36-7.17 (m, 9H), 7.12 (dd, 1H, J=7.5, 7.5 Hz), 6.67 (m, 3H), 4.97 (s, 1H), 3.76 (m, 1H), 3.57 (m, 2H), 3.42-3.16 (m, 3H), 2.75 (m, 2H), 2.69-2.49 (m, 8H), 2.37 (m, 1H), 2.31 (m, 1H), 1.98 (m, 1H), 1.90 (m, 1H), 1.79 (m, 1H), 1.63 (m, 1H), 1.01 (m, 6H).

Workup

  1. customThe mixture was put under rotary evaporator for the removal of THF
  2. additionThe remaining water layer was diluted by water (3 mL)
  3. extractionThe water layer was extracted by n-butanol (5 mL×3)
  4. washThe combined n-butanol layer was washed by water (5 mL×2)
  5. concentrationconcentrated
  6. customto give crude product (200 mg), which
  7. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-769cf14d5aeb42abbeb8c43da4f93267
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

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