Hydrochloric Acid → HCID 58815931, compound

HRID 2245877Notes

Reaction equation

HRID 2245877 reaction equation
C([O:3][C:4](=[O:42])[CH2:5][CH2:6][CH2:7][N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15](=[O:41])[C:16]2[CH:21]=[CH:20][C:19]([C@@H:22]([N:30]3[CH2:35][C@@H:34]([CH3:36])[N:33]([CH2:37][CH:38]=[CH2:39])[CH2:32][C@@H:31]3[CH3:40])[C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([OH:29])[CH:24]=3)=[CH:18][CH:17]=2)[CH2:10][CH2:9]1)C.Cl>C1COCC1.[OH-].[Na+]>[CH2:37]([N:33]1[C@H:34]([CH3:36])[CH2:35][N:30]([C@@H:22]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([OH:29])[CH:24]=2)[C:19]2[CH:18]=[CH:17][C:16]([C:15]([N:11]3[CH2:12][CH2:13][CH2:14][N:8]([CH2:7][CH2:6][CH2:5][C:4]([OH:42])=[O:3])[CH2:9][CH2:10]3)=[O:41])=[CH:21][CH:20]=2)[C@@H:31]([CH3:40])[CH2:32]1)[CH:38]=[CH2:39]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 58815879HCID 58815879, compound

Product 1

HCID 58815931HCID 58815931, compoundYield 57.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

To the compound of Example 117 (330 mg) in THF (5 mL) was added IN NaOH solution (3 mL). The reaction was stirred at room temperature overnight. The reaction solution was neutralized by the addition of 1 N HCl solution (3 mL). The organic solvent was removed under vacuum. The remaining water layer was diluted by water (4 mL). The water layer was extracted by n-butanol (10 mL×3). The combined n-butanol layer was washed by water (10 mL×2) and concentrated to give crude product (245 mg), which was purified by silica gel chromatography conducted on CombiFlash™ Sq 16×(gradient: 100% CH2Cl2 to 30% MeOH in CH2Cl2) to give 4-(4-{4-[(R)-((2S,5R)-4-allyl-2,5-dimethylpiperazin-1-yl)(3-hydroxy-phenyl)methyl]benzoyl}[1,4]diazepan-1-yl)butyric acid (180 mg; 57%). 1H NMR (300 MHz, DMSO-d6) δ 9.36 (bs, 1H), 8.31 (s, 1H), 7.40 (d, 2H, J=7.5 Hz), 7.30 (d, 2H, J=7.5 Hz), 7.12 (dd, 1H, J=8.0, 8.0 Hz), 6.66 (m, 3H), 5.78 (m, 1H), 5.20-4.97 (m, 3H), 3.59 (m, 2H), 3.47-3.34 (m, 2H), 3.18 (m, 1H), 2.86 (m, 1H), 2.73 (m, 2H), 2.60-2.49 (m, 7H), 2.42 (m, 1H), 2.21 (m, 2H), 2.10 (m, 1H), 1.83 (m, 2H), 1.69-1.55 (m, 3H), 1.06 (d, 3H, J=6.0 Hz), 0.94 (d, 3H, J=5.5 Hz).

Workup

  1. customThe organic solvent was removed under vacuum
  2. additionThe remaining water layer was diluted by water (4 mL)
  3. extractionThe water layer was extracted by n-butanol (10 mL×3)
  4. washThe combined n-butanol layer was washed by water (10 mL×2)
  5. concentrationconcentrated
  6. customto give crude product (245 mg), which
  7. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-c567af6b385d46a59e47a9031965f371
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

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