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

HRID 854849Notes

Reaction equation

HRID 854849 reaction equation
Cl.[NH2:2][OH:3].[Cl:4][C:5]1[CH:6]=[C:7]([C@@H:15]([CH2:26][CH:27]2[CH2:32][CH2:31][C:30](=O)[CH2:29][CH2:28]2)[C:16]([NH:18][C:19]2[CH:24]=[N:23][C:22]([Cl:25])=[CH:21][N:20]=2)=[O:17])[CH:8]=[CH:9][C:10]=1[S:11]([CH3:14])(=[O:13])=[O:12]>CO.N1C(C)=CC=CC=1C>[Cl:4][C:5]1[CH:6]=[C:7]([C@@H:15]([CH2:26][CH:27]2[CH2:32][CH2:31][C:30](=[N:2][OH:3])[CH2:29][CH2:28]2)[C:16]([NH:18][C:19]2[CH:24]=[N:23][C:22]([Cl:25])=[CH:21][N:20]=2)=[O:17])[CH:8]=[CH:9][C:10]=1[S:11]([CH3:14])(=[O:13])=[O:12]

Participants

5

Reactant 2

HCID 443297Hydroxyamine hydrochlorideHCID 10412416HCID 10412416, compound

Product 1

HCID 100283372(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-chloro-pyrazin-2-yl)-3-(4-hydroxyimino-cyclohexyl)-propionamideYield 93.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 79372,6-LutidineSolvent

Conditions

Temperature
25 °C

Procedure

A solution of hydroxylamine hydrochloride (7.0 mg, 0.099 mmol) in methanol (0.2 mL) and 2,6-lutidine (0.2 mL) was treated with 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-chloro-pyrazin-2-yl)-3-(4-oxo-cyclohexyl)-propionamide (prepared as in Example 61, 31 mg, 0.066 mmol). The reaction mixture was stirred at 25° C. for 30 min and was then 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 12S, Silica, 13/7 hexanes/ethyl acetate to 2/3 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-chloro-pyrazin-2-yl)-3-(4-hydroxyimino-cyclohexyl)-propionamide (30 mg, 93.7%) was a white foam: [α]23589=−23.24° (c=0.37, chloroform); EI-HRMS m/e calcd for C20H22Cl2N4O4S (M+H)+ 485.0812. found 485.0822.

Workup

  1. concentrationwas then concentrated in vacuo
  2. customto remove methanol
  3. washwashed with water 1×5 mL),
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-afe403bd1c62490fa2a3768d5843cc89
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

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