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

HRID 407887Notes

Reaction equation

HRID 407887 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[C:5]([CH3:12])=[CH:4][C:3]=1[NH:13][C@H:14]1[CH2:18][CH2:17][N:16]([CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[C:15]1=[O:25].[Cl:26][C:27]1[CH:32]=[N:31][C:30](Cl)=[CH:29][N:28]=1.C(N(C(C)C)C(C)C)C.O>CS(C)=O>[Cl:26][C:27]1[N:28]=[CH:29][C:30]([N:22]2[CH2:21][CH2:20][CH:19]([N:16]3[CH2:17][CH2:18][C@H:14]([NH:13][C:3]4[CH:4]=[C:5]([CH3:12])[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:7][C:2]=4[F:1])[C:15]3=[O:25])[CH2:24][CH2:23]2)=[N:31][CH:32]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 3362242,5-DichloropyrazineHCID 67469759(S)-3-(2-fluoro-5-methyl-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one

Product 1

HCID 54671274(S)-1-(1-(5-chloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-5-methyl-4-(methylsulfonyl)phenylamino)pyrrolidin-2-oneYield 60.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
110 °C

Procedure

(S)-3-(2-Fluoro-5-methyl-4-(methylsulfonyl)phenylamino)-1-(piperidin-4-yl)pyrrolidin-2-one (420 mg, 1.14 mmol) was dissolved in DMSO (10 mL) and 2,5-dichloropyrazine (203 mg, 1.36 mmol) and N-ethyl-N-isopropylpropan-2-amine (297 μL, 1.71 mmol) were added and the reaction heated to 110° C. overnight. The reaction was cooled to ambient temperature, water (60 mL) was added and the solids filtered. The solids were dissolved in CH2Cl2, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified over silica gel (70 to 100% EtOAc in hexanes) to afford (S)-1-(1-(5-chloropyrazin-2-yl)piperidin-4-yl)-3-(2-fluoro-5-methyl-4-(methylsulfonyl)phenylamino)pyrrolidin-2-one (330 mg, 0.685 mmol, 60.2% yield) as a pale yellow solid. Mass spectrum (apci) m/z=482.2 (M+H).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. filtrationthe solids filtered
  3. dissolutionThe solids were dissolved in CH2Cl2
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified over silica gel (70 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-33095eced88f4feeb20bfa6fc8a2170c
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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