2,6-Lutidine → N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

HRID 719912Notes

Reaction equation

HRID 719912 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH: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]([Br:35])=[CH:31][N:30]=1.N1C(C)=CC=CC=1C>C(Cl)Cl.CN(C)C=O.O1CCCC1.C(OCC)(=O)C>[Br:35][C:32]1[N:33]=[CH:34][C:29]([NH:28][C:13](=[O:15])[CH:12]([C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:9])=[O:10])=[C:2]([Cl:1])[CH:3]=2)[CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[N:30][CH:31]=1

Participants

9

Reactant 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 5995392-Amino-5-bromopyrazineHCID 120676542-(3-Chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid

Product 1

HCID 21897386N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamideYield 68%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (1.00 g, 3.023 mmol) in methylene chloride (16 mL) was cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (1.15 mL, 13.18 mmol) followed by N,N-dimethylformamide (2 drops). The reaction mixture was stirred at 0° C. for 20 min and then at 25° C. for 2 h. The solution was then concentrated in vacuo. The residue was dissolved in methylene chloride (16 mL) and cooled to 0° C. To this solution was added a solution of 2-amino-5-bromopyrazine (530.0 mg, 3.046 mmol) and 2,6-lutidine (420 μL, 3.606 mmol) in tetrahydrofuran (16 mL) over 1 min. The reaction mixture was stirred at 0° C. for 30 min and then at 25° C. for 3 h. The reaction material was then diluted with ethyl acetate and washed with a 1N aqueous hydrochloric acid solution. The aqueous layer was back-extracted with a 1N aqueous hydrochloric acid solution. The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40L, Silica, 1/3 ethyl acetate/hexanes) afforded N-(5-bromo-pyrazin-2-yl)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (1.00 g, 68%) as a white foam: (ES)+-HRMS m/e calcd for C19H21BrClN3O3S (M+H)+ 486.0249, found 486.0254.

Workup

  1. waitat 25° C. for 2 h
  2. concentrationThe solution was then concentrated in vacuo
  3. dissolutionThe residue was dissolved in methylene chloride (16 mL)
  4. temperaturecooled to 0° C
  5. stirringThe reaction mixture was stirred at 0° C. for 30 min
  6. waitat 25° C. for 3 h
  7. washwashed with a 1N aqueous hydrochloric acid solution
  8. extractionThe aqueous layer was back-extracted with a 1N aqueous hydrochloric acid solution
  9. washThe combined organic layers were washed with a saturated aqueous sodium bicarbonate solution
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e649df35f06042b79c5a8caf351f67d6
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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