2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-formyl-pyrazin-2-yl)-propionamide → 2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1-hydroxy-ethyl)-pyrazin-2-yl]-propionamide

HRID 719886Notes

Reaction equation

HRID 719886 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:24][CH:25]2[CH2:29][CH2:28][CH2:27][CH2:26]2)[C:13]([NH:15][C:16]2[CH:21]=[N:20][C:19]([CH:22]=[O:23])=[CH:18][N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[CH3:30][Mg]Cl>C(OCC)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:12]([CH2:24][CH:25]2[CH2:26][CH2:27][CH2:28][CH2:29]2)[C:13]([NH:15][C:16]2[CH:21]=[N:20][C:19]([CH:22]([OH:23])[CH3:30])=[CH:18][N:17]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

4

Reactant 2

HCID 218973302-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-formyl-pyrazin-2-yl)-propionamideHCID 178418332HCID 178418332, compound

Product 1

HCID 104565022-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1-hydroxy-ethyl)-pyrazin-2-yl]-propionamideYield 62%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-formyl-pyrazin-2-yl)-propionamide (prepared as in Example 18, 218 mg, 0.5 mmol) in diethyl ether (15 mL) at 0° C. was slowly treated with 3.0M solution of methylmagnesium chloride in diethyl ether (0.35 mL, 1.05 mmol). After complete addition, the reaction mixture was stirred at 0° C. for 1 h. The reaction was then quenched by the dropwise addition of a 1N aqueous hydrochloric acid solution. The reaction was then diluted with water (25 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (2×20 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 3/7 to 7/3 ethyl acetate/hexanes) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(1-hydroxy-ethyl)-pyrazin-2-yl]-propionamide (140 mg, 62%) as a white solid: LC-MS m/e 451 (MH+).

Workup

  1. additionAfter complete addition
  2. customThe reaction was then quenched by the dropwise addition of a 1N aqueous hydrochloric acid solution
  3. additionThe reaction was then diluted with water (25 mL)
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. washThe combined organic layers were washed with a saturated aqueous sodium chloride solution (2×20 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0fa28a3d99944500acb3de593892e358
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

Loading…