Methanol → N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-2-yloxy)phenyl]pyridin-1(2H)-yl}butanamide

HRID 84249Notes

Reaction equation

HRID 84249 reaction equation
CO.[CH3:3][C:4]([S:37]([CH3:40])(=[O:39])=[O:38])([CH2:15][CH2:16][N:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][C:26]([O:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)=[CH:25][CH:24]=2)=[CH:19][C:18]1=[O:36])[C:5]([NH:7][O:8]C1CCCCO1)=[O:6]>Cl.O1CCOCC1>[OH:8][NH:7][C:5](=[O:6])[C:4]([CH3:3])([S:37]([CH3:40])(=[O:39])=[O:38])[CH2:15][CH2:16][N:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:24]=[CH:25][C:26]([O:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)=[CH:27][CH:28]=2)=[CH:19][C:18]1=[O:36]

Participants

5

Reactant 2

HCID 887MethanolHCID 866719342-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-2-yloxy)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Product 1

HCID 86671933N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-2-yloxy)phenyl]pyridin-1(2H)-yl}butanamideYield 94.2%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

Methanol (25 mL) was added to a solution of 2-methyl-2-(methylsulfonyl)-4-{2-oxo-4-[4-(pyridin-2-yloxy)phenyl]pyridin-1(2H)-yl}-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (212 mg, 0.39 mmol) in 4.0 M hydrochloric acid in 1,4-dioxane (4.9 mL) at room temperature. After 1 h, the reaction was concentrated under reduced pressure. The resulting residue was triturated with 10:1 diethyl ether-methanol, filtered, and dried under reduced pressure to provide a white solid (168 mg, 88%). LCMS m/z 458.6 (M+1). 1H NMR (400 MHz, CD3OD) δ ppm 1.73 (s, 3H), 2.41 (ddd, J=13, 10.5, 5 Hz, 1H), 2.67 (ddd, J=13, 10.5, 5 Hz, 1H), 3.11 (s, 3H), 4.06 (ddd, J=13, 11.5 Hz, 1H), 4.39 (ddd, J=13, 11, 5 Hz, 1H), 6.97-7.00 (m, 2H), 7.25 (br d, J=8.7 Hz, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.56 (ddd, J=7.4, 5.8, 0.9 Hz, 1H), 7.90-7.94 (m, 3H), 8.33 (ddd, J=8.7, 7.4, 1.9 Hz, 1H), 8.47 (ddd, J=5.8, 1.9, 0.6 Hz, 1H).

Workup

  1. concentrationthe reaction was concentrated under reduced pressure
  2. customThe resulting residue was triturated with 10:1 diethyl ether-methanol
  3. filtrationfiltered
  4. customdried under reduced pressure

Sources & evidence

ORD record
ord-5460a7e3eb9f43fe8ebf3317ad5f902d
Source dataset
uspto-grants-2014_09
Patent number
US08846933B2

Reaction notes

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