Water → HCID 57658329, compound

HRID 1667380Notes

Reaction equation

HRID 1667380 reaction equation
[NH2:1][C:2]1[N:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[C:6](=[O:15])[CH:5]=[CH:4][C:3]=1[C:16](=[O:24])[C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1.Br[CH2:26][C:27]([NH:29][C@H:30]([C:35]([O:37][CH:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1)=[O:36])[CH2:31][CH:32]([CH3:34])[CH3:33])=[O:28].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[NH2:1][C:2]1[N:7]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH2:26][C:27]([NH:29][C@H:30]([C:35]([O:37][CH:38]3[CH2:42][CH2:41][CH2:40][CH2:39]3)=[O:36])[CH2:31][CH:32]([CH3:34])[CH3:33])=[O:28])=[CH:12][CH:13]=2)[C:6](=[O:15])[CH:5]=[CH:4][C:3]=1[C:16](=[O:24])[C:17]1[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 59139923HCID 59139923, compoundHCID 67445922HCID 67445922, compound

Product 1

HCID 57658329HCID 57658329, compoundYield 52.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-amino-5-(4-fluorobenzoyl)-1-(4-hydroxyphenyl)pyridin-2(1H)-one [WO 03/076405] (100 mg, 0.31 mmol) in anhydrous DMF (3 ml) under an atmosphere of nitrogen was added cyclopentyl N-(bromoacetyl)-L-leucinate (109 ml, 0.34 mmol, 1.1 eq) and potassium carbonate (51 mg, 0.37 mmol, 1.2 eq). The mixture was heated at 40 C for 16 hours, before being allowed to cool to room temperature and added to water (20 ml). The mixture was extracted with EtOAc (3×15 ml), and the combined extracts washed with water (2×40 ml) and brine (40 ml). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. Purification by column chromatography (2-3% MeOH in DCM) followed by trituration with minimal MeOH afforded the title compound as a white solid (91 mg, 52% yield).

Workup

  1. temperatureThe mixture was heated at 40 C for 16 hours
  2. extractionThe mixture was extracted with EtOAc (3×15 ml)
  3. washthe combined extracts washed with water (2×40 ml) and brine (40 ml)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by column chromatography (2-3% MeOH in DCM)

Sources & evidence

ORD record
ord-b10a98e3eee145de82380ef89b6e1b2f
Source dataset
uspto-grants-2011_10
Patent number
US08044211B2

Reaction notes

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