Diisopropylethylamine → (2R)-4-{5-Fluoro-4-[4-(methylthio)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 1625024Notes

Reaction equation

HRID 1625024 reaction equation
C(N(CC)C(C)C)(C)C.[O:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH:11]1[O:16][NH2:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:42][C:43]1[C:44]([C:61]2[CH:66]=[CH:65][C:64]([S:67][CH3:68])=[CH:63][CH:62]=2)=[CH:45][C:46](=[O:60])[N:47]([CH2:49][CH2:50][C@@:51]([CH3:59])([S:55]([CH3:58])(=[O:57])=[O:56])[C:52](O)=[O:53])[CH:48]=1>CN(C=O)C.CCOC(C)=O>[F:42][C:43]1[C:44]([C:61]2[CH:62]=[CH:63][C:64]([S:67][CH3:68])=[CH:65][CH:66]=2)=[CH:45][C:46](=[O:60])[N:47]([CH2:49][CH2:50][C@@:51]([CH3:59])([S:55]([CH3:58])(=[O:57])=[O:56])[C:52]([NH:17][O:16][CH:11]2[CH2:12][CH2:13][CH2:14][CH2:15][O:10]2)=[O:53])[CH:48]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 70664819(2R)-4-{5-Fluoro-4-[4-(methylthio)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanoic acid

Product 1

HCID 86670639(2R)-4-{5-Fluoro-4-[4-(methylthio)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideYield 100%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

N,N-Diisopropylethylamine (450 uL, 2.45 mmol), O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (192 mg, 1.64 mmol) and HATU (447 mg, 1.23 mmol) were added to a solution of (2R)-4-{5-fluoro-4-[4-(methylthio)phenyl]-2-oxopyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)butanoic acid (339 mg, 0.82 mmol) in DMF (10 mL). The reaction was allowed to stir at rt for 18 h. The reaction mixture was diluted with EtOAc and washed with brine. The organics were dried (MgSO4), filtered and concentrated. The crude residue was purified via flash chromatography using a 40 g silica column and an eluent of EtOAc in n-heptane (0-100%) to afford the title compound (420 mg, 100%). MS (LCMS) m/z 511.4 (M−1).

Workup

  1. washwashed with brine
  2. dry with materialThe organics were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude residue was purified via flash chromatography

Sources & evidence

ORD record
ord-2f94f4c058584709b985cd3f495a5fd9
Source dataset
uspto-grants-2014_07
Patent number
US08779148B2

Reaction notes

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