Pyridine → N-(5-allyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentylpropionamide

HRID 720009Notes

Reaction equation

HRID 720009 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.[CH2:28]([C:31]1[N:32]=[CH:33][C:34]([NH2:37])=[N:35][CH:36]=1)[CH:29]=[CH2:30].N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.C(OCC)(=O)C>[CH2:28]([C:31]1[N:32]=[CH:33][C:34]([NH:37][C:13](=[O:15])[C@@H: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:35][CH:36]=1)[CH:29]=[CH2:30]

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acidHCID 218973655-Allylpyrazin-2-amine

Product 1

HCID 67482647N-(5-allyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentylpropionamideYield 89.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 800.0 mg, 2.418 mmol) in methylene chloride (12 mL) cooled to 0° C. under nitrogen was treated with oxalyl chloride (0.64 mL, 7.336 mmol), followed by N,N-dimethylformamide (2 drops). The reaction mixture was stirred at 0° C. for 20 min and then stirred at 25° C. for 1.25 h. The reaction mixture was concentrated in vacuo. The residue was dissolved in methylene chloride (12 mL), cooled to 0° C. under nitrogen, and then treated with a solution of 5-allyl-pyrazin-2-ylamine (0.37 g, 2.737 mmol) and pyridine (0.59 mL, 7.295 mmol) in methylene chloride (12 mL) over 1 min. The resulting reaction mixture was stirred at 0° C. for 30 min and then at 25° C. for 1 h. The reaction mixture was then diluted with ethyl acetate and washed with a 1N aqueous hydrochloric acid solution. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH, 40L, Silica, 1/1 hexanes/ethyl acetate) afforded N-(5-allyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentylpropionamide (965 mg, 89.1%) as a white foam: LRMS for C22H26ClN3O3S (M−H)+ at m/z=446

Workup

  1. stirringstirred at 25° C. for 1.25 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in methylene chloride (12 mL)
  4. temperaturecooled to 0° C. under nitrogen
  5. customThe resulting reaction mixture
  6. stirringwas stirred at 0° C. for 30 min
  7. waitat 25° C. for 1 h
  8. washwashed with a 1N aqueous hydrochloric acid solution
  9. extractionThe aqueous layer was extracted with ethyl acetate
  10. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-86fb555af10144f98ca451947998da0c
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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