Trifluoroacetic acid → (2R)-2-(3-chloro-4-methylsulfonylphenyl)-3-cyclopentyl-N-[5-[(Z)-N-hydroxy-C-methylcarbonimidoyl]pyrazin-2-yl]propanamide

HRID 719894Notes

Reaction equation

HRID 719894 reaction equation
C([O:5][N:6]=[C:7]([C:9]1[N:10]=[CH:11][C:12]([NH:15][C:16](=[O:35])[C@@H:17]([C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[C:26]([Cl:34])[CH:25]=2)[CH2:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)=[N:13][CH:14]=1)[CH3:8])(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl.C(OCC)(=O)C>[Cl:34][C:26]1[CH:25]=[C:24]([C@@H:17]([CH2:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[C:16]([NH:15][C:12]2[CH:11]=[N:10][C:9](/[C:7](=[N:6]\[OH:5])/[CH3:8])=[CH:14][N:13]=2)=[O:35])[CH:29]=[CH:28][C:27]=1[S:30]([CH3:33])(=[O:32])=[O:31]

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86593784N-[5-(1-tert-butoxyimino-ethyl)-pyrazin-2-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

Product 1

HCID 135474732(2R)-2-(3-chloro-4-methylsulfonylphenyl)-3-cyclopentyl-N-[5-[(Z)-N-hydroxy-C-methylcarbonimidoyl]pyrazin-2-yl]propanamideYield 63%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of N-[5-(1-tert-butoxyimino-ethyl)-pyrazin-2-yl]-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (195.5 mg, 0.38 mmol) in methylene chloride (1.4 mL) was treated with trifluoroacetic acid (2.8 mL). The resulting reaction mixture was stirred at 25° C. for 2 h, at which time, thin layer chromatography still indicated the presence of starting material. The reaction was then heated at 40° C. where it was stirred overnight. At this time, thin layer chromatography again still indicated the presence of starting material. The reaction mixture was then heated at 60° C. where it was stirred for a second night. The reaction mixture was then allowed cool to 25° C. The reaction mixture was diluted with ethyl acetate (50 mL), and the organic layer was washed with a saturated aqueous sodium bicarbonate solution (2×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40L, Silica, 1/2 ethyl acetate/hexanes) afforded the 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1(Z)-hydroxyimino-ethyl)-pyrazin-2-yl]-propionamide (110.0 mg, 63%) as an off-white powdery solid: mp 94.2–102.5° C. (foam to gel); (ES)+-HRMS m/e calcd for C21H25ClN4O4S (M+H)+ 465.1358, found 465.1363.

Workup

  1. customThe resulting reaction mixture
  2. temperatureThe reaction was then heated at 40° C. where it
  3. stirringwas stirred overnight
  4. temperatureThe reaction mixture was then heated at 60° C. where it
  5. stirringwas stirred for a second night
  6. temperatureThe reaction mixture was then allowed cool to 25° C
  7. washthe organic layer was washed with a saturated aqueous sodium bicarbonate solution (2×50 mL)
  8. dry with materiala saturated aqueous sodium chloride solution (1×50 mL), dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fe74f011e28644ae8a49e63fd376eb20
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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