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

HRID 854847Notes

Reaction equation

HRID 854847 reaction equation
Cl.[NH2:2][OH:3].[Br:4][C:5]1[N:6]=[CH:7][C:8]([NH:11][C:12](=[O:33])[CH:13]([C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[C:24]([Cl:32])[CH:23]=2)[CH2:14][CH:15]2[CH2:20][CH2:19][C:18](=O)[CH2:17][CH2:16]2)=[N:9][CH:10]=1>CO.N1C=CC=CC=1>[Br:4][C:5]1[N:6]=[CH:7][C:8]([NH:11][C:12](=[O:33])[CH:13]([C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[C:24]([Cl:32])[CH:23]=2)[CH2:14][CH:15]2[CH2:20][CH2:19][C:18](=[N:2][OH:3])[CH2:17][CH2:16]2)=[N:9][CH:10]=1

Participants

5

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 10029482N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-oxo-cyclohexyl)-propionamide

Product 1

HCID 10324704N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-hydroxyimino-cyclohexyl)-propionamideYield 80.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

A solution of hydroxylamine hydrochloride (13 mg, 0.18 mmol) in methanol (0.5 mL) and pyridine (0.5 mL) was treated with N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-oxo-cyclohexyl)-propionamide (prepared as in Example 59, 62 mg, 0.12 mmol). The reaction mixture was heated under reflux for 2 h, cooled to 25° C., and concentrated in vacuo to remove methanol. The resulting residue was suspended in ethyl acetate (10 mL), washed with water 1×5 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 3/7 hexanes/ethyl acetate eluted to 8/2 hexanes/ethyl acetate) afforded the N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-hydroxyimino-cyclohexyl)-propionamide (51 mg, 80%) as a white foam: EI-HRMS m/e calcd for C20H22BrClN4O4S (M+H)+ 529.0307. found 529.0308.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureunder reflux for 2 h
  3. concentrationconcentrated in vacuo
  4. customto remove methanol
  5. washwashed with water 1×5 mL),
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. washBiotage chromatography (FLASH 12M, Silica, 3/7 hexanes/ethyl acetate eluted to 8/2 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-4bab3aac63ce48d994c59026a79516bc
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

Loading…