Acetic Anhydride → HCID 44462999, compound

HRID 241632Notes

Reaction equation

HRID 241632 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[N:8]([C:20]3[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][C:21]=3[F:27])[C:9]3[C:14]([C:15]=2/[C:16](=[N:18]/O)/[NH2:17])=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:28])[O:4][N:3]=1.C(OC(=O)C)(=O)C>C(O)(=O)C.[Pd]>[CH3:1][C:2]1[C:6]([C:7]2[N:8]([C:20]3[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][C:21]=3[F:27])[C:9]3[C:14]([C:15]=2[C:16](=[NH:17])[NH2:18])=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:28])[O:4][N:3]=1

Participants

5

Reactant 2

HCID 7918Acetic AnhydrideHCID 58378226HCID 58378226, compound

Product 1

HCID 44462999HCID 44462999, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

0.5 mmol (Z)-2-(3,5-dimethylisoxazol-4-yl)-1-(2-fluoro-4-hydroxyphenyl)-N′-hydroxy-1H-indole-3-carboximidamide (Example 235) was dissolved in 5 ml acetic acid. Acetic acid anhydride (4 eq) was slowly added and the mixture was stirred over night. A Pd—C catalyst (10% on carbon) was added and the mixture was placed in a hydrogenation apparatus under 50 psi H2 over night. The mixture was filtered through celite and concentrated. The crude product was purified on HPLC: (Column: Sunfire, 20 min acidic gradient: 5-50% MeCN. ES/MS m/z: 365.15 (M+H), 363.18 (M−H); 1H NMR (MeOD, 500 MHz): 7.86 (m, 1H), 7.41-7.31 (m, 2.5H), 7.25-7.13 (m, 1.5H), 6.76 (m, 1H), 6.67 (m, 1H), 2.21, 2.15 (two s, 3H) and 2.08, 2.06 (two s, 3H).

Workup

  1. waitthe mixture was placed in a hydrogenation apparatus under 50 psi H2 over night
  2. filtrationThe mixture was filtered through celite
  3. concentrationconcentrated
  4. customThe crude product was purified on HPLC
  5. customSunfire, 20 min acidic gradient

Sources & evidence

ORD record
ord-96a2227e05e74944bf995d61fa69a927
Source dataset
uspto-grants-2014_02
Patent number
US08653072B2

Reaction notes

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