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

HRID 854824Notes

Reaction equation

HRID 854824 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:22][CH:23]2[CH2:27][CH2:26][C:25](=O)[CH2:24]2)[C:13]([NH:15][C:16]2[CH:21]=[N:20][CH:19]=[CH:18][N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].Cl.[NH2:30][OH:31]>CO.N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:22][CH:23]2[CH2:27][CH2:26][C:25](=[N:30][OH:31])[CH2:24]2)[C:13]([NH:15][C:16]2[CH:21]=[N:20][CH:19]=[CH:18][N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9]

Participants

5

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 10477292Piragliatin;RO 4389620

Product 1

HCID 851540592-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-hydroxyimino-cyclopentyl)-N-pyrazin-2-yl-propionamideYield 55%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-oxo-cyclopentyl)-N-pyrazin-2-yl-propionamide (prepared as in Example 45, 121.9 mg, 0.29 mmol) and hydroxylamine hydrochloride (30.4 mg, 0.43 mmol) in methanol (0.85 mL) and pyridine (0.85 mL) was heated under reflux for 5 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 layer was washed with a 1N aqueous hydrochloric acid solution (2×50 mL) and a saturated aqueous sodium chloride solution (50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 80-100% ethyl acetate/hexanes) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(3-hydroxyimino-cyclopentyl)-N-pyrazin-2-yl-propionamide (68.8 mg, 55%) as a white solid: mp 205-207° C.; (ES)+-HRMS m/e calcd for C19H21ClN4O4S (M+H)+ 437.1045. found 437.1048.

Workup

  1. temperatureunder reflux for 5 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 layer was washed with a 1N aqueous hydrochloric acid solution (2×50 mL)
  6. dry with materiala saturated aqueous sodium chloride solution (50 mL), dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-80372320c50b43e19d7251abe46c399a
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

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