Cesium carbonate → 1-Methyl-4-(2-(4-(pyridin-2-ylamino)phenoxy)pyridin-3-yl)pyrrolidin-2-one

HRID 473733Notes

Reaction equation

HRID 473733 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[N:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[NH:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.F[C:22]1[C:27]([CH:28]2[CH2:32][N:31]([CH3:33])[C:30](=[O:34])[CH2:29]2)=[CH:26][CH:25]=[CH:24][N:23]=1>CN1C(=O)CCC1>[CH3:33][N:31]1[CH2:32][CH:28]([C:27]2[C:22]([O:20][C:17]3[CH:18]=[CH:19][C:14]([NH:13][C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][N:7]=4)=[CH:15][CH:16]=3)=[N:23][CH:24]=[CH:25][CH:26]=2)[CH2:29][C:30]1=[O:34]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 212625714-(Pyridin-2-ylamino)phenolHCID 593270184-(2-Fluoropyridin-3-yl)-1-methylpyrrolidin-2-one

Product 1

HCID 593740621-Methyl-4-(2-(4-(pyridin-2-ylamino)phenoxy)pyridin-3-yl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of cesium carbonate (0.559 g, 1.72 mmol), 4-(pyridin-2-ylamino)phenol (0.320 g, 1.72 mmol), and 4-(2-fluoropyridin-3-yl)-1-methylpyrrolidin-2-one (0.110 g, 0.566 mmol) was added NMP (2 mL). The reaction mixture was degassed and heated to 100° C. for 2 h. The reaction mixture was diluted with EtOAc and water. The aqueous phase was extracted with EtOAc (4×) and the combined organic extracts were washed with 1 M NaOH (1×), brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (30% to 100% EtOAc (10% MeOH) in hexanes) gave 1-methyl-4-(2-(4-(pyridin-2-ylamino)phenoxy)pyridin-3-yl)pyrrolidin-2-one as a white solid and a 1:1 mixture of enantiomers. MS (ESI, pos. ion) m/z: 361.1 (M+1). IC50 (uM) 0.01406.

Workup

  1. customThe reaction mixture was degassed
  2. additionThe reaction mixture was diluted with EtOAc and water
  3. extractionThe aqueous phase was extracted with EtOAc (4×)
  4. washthe combined organic extracts were washed with 1 M NaOH (1×), brine (1×)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash column chromatography on silica gel (30% to 100% EtOAc (10% MeOH) in hexanes)

Sources & evidence

ORD record
ord-af691c06172b47daa87388990c15a181
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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