Hydroxyamine hydrochloride → N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-hydroxyimino-cyclopentyl)-propionamide

HRID 2214116Notes

Reaction equation

HRID 2214116 reaction equation
[Br:1][C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9](=[O:29])[CH:10]([C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[C:20]([Cl:28])[CH:19]=2)[CH2:11][CH:12]2[CH2:16][CH2:15][C:14](=O)[CH2:13]2)=[N:6][CH:7]=1.Cl.[NH2:31][OH:32]>CO.N1C=CC=CC=1>[Br:1][C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9](=[O:29])[CH:10]([C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[C:20]([Cl:28])[CH:19]=2)[CH2:11][CH:12]2[CH2:16][CH2:15][C:14](=[N:31][OH:32])[CH2:13]2)=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 9983474N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclopentyl)-propionamide

Product 1

HCID 85082842N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-hydroxyimino-cyclopentyl)-propionamideYield 77%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

A solution of N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclopentyl)-propionamide (prepared as in Example 49, 190 mg, 0.38 mmol) and hydroxylamine hydrochloride (40 mg, 0.57 mmol) in methanol (0.90 mL) and pyridine (0.90 mL) was heated under reflux for 3 h. The reaction mixture was allowed to cool to 25° C. and was then concentrated in vacuo. The resulting residue was diluted with water (50 mL) and extracted with ethyl acetate (50 mL). The organic layers were washed with a 1N aqueous hydrochloric acid solution (50 mL) and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 75% ethyl acetate/hexanes) afforded the N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-hydroxyimino-cyclopentyl)-propionamide 77%) as a yellow foam: mp 100–106° C.; (ES)+-HRMS m/e calcd for C19H20BrClN4O4S (M+H)+ 515.0150 found 515.0154.

Workup

  1. temperatureunder reflux for 3 h
  2. concentrationwas then concentrated in vacuo
  3. additionThe resulting residue was diluted with water (50 mL)
  4. extractionextracted with ethyl acetate (50 mL)
  5. washThe organic layers were washed with a 1N aqueous hydrochloric acid solution (50 mL)
  6. dry with materiala saturated aqueous sodium chloride solution, dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ce136d87a50443f1b79b350a7657c8e7
Source dataset
uspto-grants-2006_09
Patent number
US07105671B2

Reaction notes

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