Pyridine → 3-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-phenyl)-N-(5-vinyl-pyrazin-2-yl)-propionamide

HRID 719967Notes

Reaction equation

HRID 719967 reaction equation
[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[C:13]([CH3:21])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:28][C:29]1[CH:34]=[N:33][C:32]([CH:35]=[CH2:36])=[CH:31][N:30]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O>[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[C:13]([CH3:21])[CH:12]=2)[C:8]([NH:28][C:29]2[CH:34]=[N:33][C:32]([CH:35]=[CH2:36])=[CH:31][N:30]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 218972565-Vinylpyrazin-2-amineHCID 671900253-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-pheny)-propionic acid

Product 1

HCID 674826383-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-phenyl)-N-(5-vinyl-pyrazin-2-yl)-propionamideYield 63%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 3-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-pheny)-propionic acid (prepared as in Example 57, 465 mg, 1.5 mmol) in methylene chloride (20 mL) was treated with oxalyl chloride (0.3 mL, 3.4 mmol) and N,N-dimethylformamide (1–2 drops). The solution was stirred at 0° C. for 5 min and then at 25° C. for 15 min. The reaction mixture was concentrated in vacuo. The residue was dissolved in methylene chloride (20 mL), cooled to 0° C., and then treated with a solution of 2-amino-5-vinylpyrazine (prepared as in Example 54, 182 mg, 1.5 mmol) and pyridine (0.37 mL, 4.6 mmol) in methylene chloride (5 mL). The mixture was stirred at 0° C. then stirred at 25° C. overnight. The solution was diluted with methylene chloride (25 mL). The organic layer was washed with a 1N aqueous sodium hydroxide solution (25 mL) and a 1N aqueous hydrochloric acid solution (25 mL). Each aqueous phase was back-extracted with a small volume of methylene chloride. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1/3 to 1/1 ethyl acetate/hexanes) afforded 3-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-phenyl)-N-(5-vinyl-pyrazin-2-yl)-propionamide (385 mg, 63%) as a white foam: (ES)+-HRMS m/e calcd for C22H27N3O3S (M+H)+ 414.1846, found 414.1849.

Workup

  1. waitat 25° C. for 15 min
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in methylene chloride (20 mL)
  4. temperaturecooled to 0° C.
  5. stirringThe mixture was stirred at 0° C.
  6. stirringthen stirred at 25° C. overnight
  7. washThe organic layer was washed with a 1N aqueous sodium hydroxide solution (25 mL)
  8. extractionEach aqueous phase was back-extracted with a small volume of methylene chloride
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f9aea169064c4dd19f5e05ba96169101
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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