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

HRID 854848Notes

Reaction equation

HRID 854848 reaction equation
Cl.[NH2:2][OH:3].[Br:4][C:5]1[N:6]=[CH:7][C:8]([NH:11][C:12](=[O:33])[C@@H: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(C)=CC=CC=1C>[Br:4][C:5]1[N:6]=[CH:7][C:8]([NH:11][C:12](=[O:33])[C@@H: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 10075193HCID 10075193, compound

Product 1

HCID 10052711N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-hydroxyimino-cyclohexyl)-propionamideYield 85.8%

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 N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-oxo-cyclohexyl)-propionamide (prepared as in Example 60, 34 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 12M, Silica, 65/35 hexanes/ethyl acetate to 2/3 hexanes/ethyl acetate) afforded the N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-hydroxyimino-cyclohexyl)-propionamide (30 mg, 85.8%) was a white foam: [α]23589=−21.43° (c=0.35, chloroform); EI-HRMS m/e calcd for C20H22BrClN4O4S (M+H)+ 529.0307. found 529.0314.

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-115d880f5b1f4026a02b8f4c3279fd48
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

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