Sodium Iodide → HCID 57658405, compound

HRID 1667378Notes

Reaction equation

HRID 1667378 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:33])[C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=1[F:32].Cl.[NH2:35][C@H:36]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:38]([CH3:40])[CH3:39].[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:35][C@H:36]([C:41]([O:43][C:44]([CH3:46])([CH3:45])[CH3:47])=[O:42])[CH2:37][CH:38]([CH3:40])[CH3:39])=[CH:10][C:9]=2[F:22])[C:6](=[O:23])[CH:5]=[CH:4][C:3]=1[C:24](=[O:33])[C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=1[F:32]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 12451443tert-butyl (2S)-2-amino-4-methylpentanoate hydrochlorideHCID 57658448HCID 57658448, compound2×

Product 1

HCID 57658405HCID 57658405, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

From Intermediate 4G. To a solution of 6-Amino-1-{4-[(5-chloropentyl)oxy]-2,6-difluorophenyl}-5-(2,4-difluorobenzoyl)pyridin-2(1H)-one (96 mg, 0.20 mmol) in anhydrous DMF (3 ml) under an atmosphere of nitrogen was added tert-butyl L-leucinate hydrochloride (198 mg, 0.99 mmol, 5 eq), sodium iodide (60 mg, 0.40 mmol, 2 eq) and N,N-diisopropylethylamine (0.072 ml, 0.40 mmol, 2 eq). The mixture was heated at 90° C. for 20 hours, before being allowed to cool to room temperature and diluted with EtOAc (20 ml). The solution was washed with water (2×20 ml) and brine (20 ml). The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. Purification by column chromatography (1-3% MeOH in DCM) followed by preparative HPLC afforded the title compound as a white solid (23 mg, 18% yield).

Workup

  1. temperatureto cool to room temperature
  2. washThe solution was washed with water (2×20 ml) and brine (20 ml)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by column chromatography (1-3% MeOH in DCM)

Sources & evidence

ORD record
ord-2149f8f6ab9949cc896afa7351dc8476
Source dataset
uspto-grants-2011_10
Patent number
US08044211B2

Reaction notes

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