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

HRID 719965Notes

Reaction equation

HRID 719965 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]([Br:35])=[CH:31][N:30]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O>[Br:35][C:32]1[N:33]=[CH:34][C:29]([NH:28][C:8](=[O:10])[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)[CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)=[N:30][CH:31]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 5995392-Amino-5-bromopyrazineHCID 671900253-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-pheny)-propionic acid

Product 1

HCID 86593795N-(5-bromo-pyrazin-2-yl)-3-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-pheny)-propionamideYield 84%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-pheny)-propionic acid (310 mg, 1.0 mmol) in methylene chloride (5 mL) was treated with oxalyl chloride (0.175 mL, 2.0 mmol) and N,N-dimethylformamide (1 drop). The solution was stirred at 25° C. for 45 min. The reaction mixture was concentrated in vacuo, and the residue was suspended in toluene. The toluene was further concentrated in vacuo. The resulting residue was dried in vacuo. The waxy material was dissolved in methylene chloride (5 mL), cooled to 0° C., and then treated with a solution of 2-amino-5-bromopyrazine (1.74 g, 1.0 mmol) and pyridine (0.121 mL, 1.5 mmol) in methylene chloride (5 mL). The mixture was stirred at 0° C. for 20 min and then stirred at 25° C. for 3 h. The solution was extracted with methylene chloride and water. The organic layer was washed with a 1N aqueous hydrochloric acid solution, a saturated aqueous sodium chloride solution, a saturated aqueous sodium bicarbonate solution, and a saturated aqueous sodium chloride solution. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1/2 ethyl acetate/hexanes) afforded the N-(5-bromo-pyrazin-2-yl)-3-cyclopentyl-2(R)-(4-methanesulfonyl-3-methyl-pheny)-propionamide (391 mg, 84%) as a fluffy solid.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. concentrationThe toluene was further concentrated in vacuo
  3. customThe resulting residue was dried in vacuo
  4. dissolutionThe waxy material was dissolved in methylene chloride (5 mL)
  5. temperaturecooled to 0° C.
  6. stirringThe mixture was stirred at 0° C. for 20 min
  7. stirringstirred at 25° C. for 3 h
  8. extractionThe solution was extracted with methylene chloride and water
  9. washThe organic layer was washed with a 1N aqueous hydrochloric acid solution
  10. dry with materialThe organic layer was dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7c718e8fd1c3449bbc8a389d2c24a60b
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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