Sodium Iodide → Cyclopentyl N-(5-{4-[6-amino-5-(4-fluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenoxy}pentyl)-L-leucinate

HRID 1667379Notes

Reaction equation

HRID 1667379 reaction equation
[NH2:1][C:2]1[N:7]([C:8]2[C:13]([F:14])=[CH:12][C:11]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]Cl)=[CH:10][C:9]=2[F:22])[C:6](=[O:23])[CH:5]=[CH:4][C:3]=1[C:24](=[O:32])[C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1.[CH:33]1([O:38][C:39](=[O:46])[C@H:40]([CH2:42][CH:43]([CH3:45])[CH3:44])[NH2:41])[CH2:37][CH2:36][CH2:35][CH2:34]1.[I-].[Na+].C(N(CC)C(C)C)(C)C>CN(C=O)C.CCOC(C)=O>[NH2:1][C:2]1[N:7]([C:8]2[C:13]([F:14])=[CH:12][C:11]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][NH:41][C@H:40]([C:39]([O:38][CH:33]3[CH2:34][CH2:35][CH2:36][CH2:37]3)=[O:46])[CH2:42][CH:43]([CH3:45])[CH3:44])=[CH:10][C:9]=2[F:22])[C:6](=[O:23])[CH:5]=[CH:4][C:3]=1[C:24](=[O:32])[C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 53718217(S)-cyclopentyl 2-amino-4-methylpentanoate2×HCID 576583306-amino-1-{4-[(5-chloropentyl)oxy]-2,6-difluorophenyl}-5-(4-fluorobenzoyl)pyridin-2(1H)-one2×

Product 1

HCID 24798351Cyclopentyl N-(5-{4-[6-amino-5-(4-fluorobenzoyl)-2-oxopyridin-1(2H)-yl]-3,5-difluorophenoxy}pentyl)-L-leucinateYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

From Intermediate 4H. To a solution of 6-amino-1-{4-[(5-chloropentyl)oxy]-2,6-difluorophenyl}-5-(4-fluorobenzoyl)pyridin-2(1H)-one (99 mg, 0.21 mmol) in anhydrous DMF (3 ml) under an atmosphere of nitrogen was added cyclopentyl L-leucinate (Intermediate 8) (212 mg, 1.06 mmol, 5 eq), sodium iodide (64 mg, 0.43 mmol, 2 eq) and N,N-diisopropylethylamine (0.039 ml, 0.21 mmol, 1 eq). The mixture was heated at 90° C. for 20 hours, before being allowed to cool to room temperature and diluted with EtOAc (25 ml). The solution was washed with water (2×25 ml) and brine (25 ml). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. Purification by column chromatography (2% MeOH in DCM) followed by preparative HPLC afforded the title compound as a yellow solid (64 mg, 48% yield).

Workup

  1. temperatureto cool to room temperature
  2. washThe solution was washed with water (2×25 ml) and brine (25 ml)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by column chromatography (2% MeOH in DCM)

Sources & evidence

ORD record
ord-17ba79c5435d4e4298062c6d67aa6dd0
Source dataset
uspto-grants-2011_10
Patent number
US08044211B2

Reaction notes

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