O-Methylhydroxylamine hydrochloride → N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-methoxyimino-cyclohexyl)-propionamide

HRID 854854Notes

Reaction equation

HRID 854854 reaction equation
Cl.[O:2]([NH2:4])[CH3:3].[Br:5][C:6]1[N:7]=[CH:8][C:9]([NH:12][C:13](=[O:34])[CH:14]([C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[C:25]([Cl:33])[CH:24]=2)[CH2:15][CH:16]2[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]2)=[N:10][CH:11]=1>CO.N1C=CC=CC=1>[Br:5][C:6]1[N:7]=[CH:8][C:9]([NH:12][C:13](=[O:34])[CH:14]([C:23]2[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:30])=[O:31])=[C:25]([Cl:33])[CH:24]=2)[CH2:15][CH:16]2[CH2:21][CH2:20][C:19](=[N:4][O:2][CH3:3])[CH2:18][CH2:17]2)=[N:10][CH:11]=1

Participants

5

Reactant 2

HCID 521874O-Methylhydroxylamine hydrochlorideHCID 10029482N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-oxo-cyclohexyl)-propionamide

Product 1

HCID 21958984N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-methoxyimino-cyclohexyl)-propionamideYield 80%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Conditions

Temperature
25 °C

Procedure

A solution of methoxylamine hydrochloride (16 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, 7/3 hexanes/ethyl acetate eluted to 4/6 hexanes/ethyl acetate) afforded the N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-methoxyimino-cyclohexyl)-propionamide (51 mg, 80%) as a white foam: EI-HRMS m/e calcd for C21H24BrClN4O4S (M+H)+ 543.0463. found 543.0464.

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, 7/3 hexanes/ethyl acetate eluted to 4/6 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-3b7920bd5b8049d183fccc17107260f6
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

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