Diethyl Ether → (S)-1-(1-(5-chloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one

HRID 407892Notes

Reaction equation

HRID 407892 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:12][C@H:13]1[CH2:17][CH2:16][N:15]([CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[C:14]1=[O:24].CCN(C(C)C)C(C)C.[Cl:34][C:35]1[CH:40]=[N:39][C:38](Cl)=[CH:37][N:36]=1.C(OCC)C>CN(C=O)C>[Cl:34][C:35]1[N:36]=[CH:37][C:38]([N:21]2[CH2:22][CH2:23][CH:18]([N:15]3[CH2:16][CH2:17][C@H:13]([NH:12][C:3]4[CH:4]=[CH:5][C:6]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:7][C:2]=4[F:1])[C:14]3=[O:24])[CH2:19][CH2:20]2)=[N:39][CH:40]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 81531DiisopropylethylamineHCID 3362242,5-DichloropyrazineHCID 66800375(S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one

Product 1

HCID 54671276(S)-1-(1-(5-chloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)pyrrolidin-2-oneYield 73.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (S)-3-(2-fluoro-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (Preparation E; 3 g, 8.44 mmol) and DIEA (7.35 mL, 42.2 mmol) in DMF (30 mL) was added 2,5-dichloropyrazine (2.51 g, 16.9 mmol). This mixture was degassed with nitrogen for 30 minutes then stirred at 100° C. for 4 hours under nitrogen. The mixture was poured into brine (500 mL) and extracted into ethyl acetate (3×100 mL). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give an oil. Diethyl ether (200 mL) was added and a precipitate formed overnight. The ether was decanted and the solid was triturated using ethanol (100 mL) at reflux with stirring for 5 minutes. The suspension was filtered and the solid was washed using ethanol to give a solid crystal. This solid was dried over the weekend under high vacuum to provide the title compound (2.9 g, 73% yield). Mass spectrum (apci) m/z=468.1 (M+H).

Workup

  1. customThis mixture was degassed with nitrogen for 30 minutes
  2. additionThe mixture was poured into brine (500 mL)
  3. extractionextracted into ethyl acetate (3×100 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oil
  8. customa precipitate formed overnight
  9. customThe ether was decanted
  10. customthe solid was triturated
  11. temperatureat reflux
  12. stirringwith stirring for 5 minutes
  13. filtrationThe suspension was filtered
  14. washthe solid was washed
  15. customto give a solid crystal
  16. customThis solid was dried over the weekend under high vacuum

Sources & evidence

ORD record
ord-44df753e96d141ae985fa602180adc57
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

Loading…