Sodium Iodide → HCID 24798259, compound

HRID 1667377Notes

Reaction equation

HRID 1667377 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].[CH:34]1([O:39][C:40](=[O:47])[C@H:41]([CH2:43][CH:44]([CH3:46])[CH3:45])[NH2:42])[CH2:38][CH2:37][CH2:36][CH2:35]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:42][C@H:41]([C:40]([O:39][CH:34]3[CH2:35][CH2:36][CH2:37][CH2:38]3)=[O:47])[CH2:43][CH:44]([CH3:46])[CH3:45])=[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 53718217(S)-cyclopentyl 2-amino-4-methylpentanoate2×HCID 57658448HCID 57658448, compound2×

Product 1

HCID 24798259HCID 24798259, compoundYield 52%

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 (138 mg, 0.29 mmol) in anhydrous DMF (3 ml) under an atmosphere of nitrogen was added cyclopentyl L-leucinate (Intermediate 8) (284 mg, 1.43 mmol, 5 eq), sodium iodide (86 mg, 0.57 mmol, 2 eq) and N,N-diisopropylethylamine (0.052 ml, 0.29 mmol, 1 eq). The mixture was heated at 90° C. for 16 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 (3-4% MeOH in DCM) followed by preparative HPLC afforded the title compound as a cream coloured solid (96 mg, 52% 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 (3-4% MeOH in DCM)

Sources & evidence

ORD record
ord-47f5de055aca467081eb92f6d2fb5848
Source dataset
uspto-grants-2011_10
Patent number
US08044211B2

Reaction notes

Loading…