Pyridine → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2-methylpropenyl)-pyrazin-2-yl]-propionamide

HRID 719976Notes

Reaction equation

HRID 719976 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.[NH2:28][C:29]1[CH:34]=[N:33][C:32]([CH:35]=[C:36]([CH3:38])[CH3:37])=[CH:31][N:30]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([NH:28][C:29]2[CH:34]=[N:33][C:32]([CH:35]=[C:36]([CH3:38])[CH3:37])=[CH:31][N:30]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acidHCID 218972945-(2-Methylprop-1-en-1-yl)pyrazin-2-amine

Product 1

HCID 674827762(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2-methylpropenyl)-pyrazin-2-yl]-propionamideYield 85%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 930 mg, 2.82 mmol) in methylene chloride (10 mL) was treated with oxalyl chloride (490 μL, 5.64 mmol) and N,N-dimethylformamide (1 drop). The mixture was stirred at 25° C. for 2 h. The reaction mixture was concentrated in vacuo, and the residue was dried in vacuo. The residue was then dissolved in benzene, and the solvents were concentrated in vacuo. The residue was dried in vacuo. This material was dissolved in methylene chloride (10 mL), cooled to 0° C., and then treated with a mixture of 2-amino-5-(2,2-dimethylvinyl)-pyrazine (420 mg, 2.82 mmol) and pyridine (340 μL) in methylene chloride (10 mL). The ice bath was removed, and the solution was stirred at 25° C. overnight. The mixture was extracted with methylene chloride and a 0.1N aqueous hydrochloric acid solution. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 2/1 hexanes/ethyl acetate) afforded the 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2-methylpropenyl)-pyrazin-2-yl]-propionamide (1.10 g, 85%) as a light yellow foam.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was dried in vacuo
  3. dissolutionThe residue was then dissolved in benzene
  4. concentrationthe solvents were concentrated in vacuo
  5. customThe residue was dried in vacuo
  6. dissolutionThis material was dissolved in methylene chloride (10 mL)
  7. temperaturecooled to 0° C.
  8. customThe ice bath was removed
  9. stirringthe solution was stirred at 25° C. overnight
  10. extractionThe mixture was extracted with methylene chloride
  11. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7bb34ed527ba46748ec0594e6a90b055
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

Loading…