Water → N-[(1R)-1-(5-fluoro-2-pyridinyl)ethyl]-3-[(E)-hydroxyiminomethyl]-5-(5-methyl-2-pyridinyl)benzamide

HRID 1257543Notes

Reaction equation

HRID 1257543 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([NH:10][C:11](=[O:27])[C:12]2[CH:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][N:19]=3)[CH:15]=[C:14]([CH:25]=O)[CH:13]=2)[CH3:9])=[N:6][CH:7]=1.O1CCOCC1.N1C=CC=CC=1.[Cl-].[NH4+:41].[OH2:42]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([NH:10][C:11](=[O:27])[C:12]2[CH:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][N:19]=3)[CH:15]=[C:14](/[CH:25]=[N:41]/[OH:42])[CH:13]=2)[CH3:9])=[N:6][CH:7]=1

Participants

6

Reactant 5

HCID 962WaterHCID 1049PyridineHCID 25517Ammonium ChlorideHCID 312751,4-DioxaneHCID 86649645HCID 86649645, compound

Product 1

HCID 87195802N-[(1R)-1-(5-fluoro-2-pyridinyl)ethyl]-3-[(E)-hydroxyiminomethyl]-5-(5-methyl-2-pyridinyl)benzamide

Conditions

Temperature
70 °C

Procedure

To a solution of N-[(1R)-1-(5-fluoro-2-pyridinyl)ethyl]-3-formyl-5-(5-methyl-2-pyridinyl)benzamide (1.10 g, 3.01 mmol) in dioxane (15 mL) hydroxylamine hydrochloride salt (0.314 g, 4.52 mmol) and pyridine (0.73 mL, 9.04 mmol). The reaction mixture was stirred at 70° C. for 18 h. The mixture was cooled to ambient temperature. Saturated aqueous ammonium chloride and water were added. The mixture was extracted with dichloromethane (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (95% dichloromethane/methanol→85% dichloromethane/methanol) gave the title compound (0.91 g). MS 379.1 (M+1).

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. extractionThe mixture was extracted with dichloromethane (3×)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (95% dichloromethane/methanol→85% dichloromethane/methanol)

Sources & evidence

ORD record
ord-a808728829604b97b6336c1d39988188
Source dataset
uspto-grants-2013_06
Patent number
US08461185B2

Reaction notes

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