Cesium carbonate → HCID 59373995, compound

HRID 473728Notes

Reaction equation

HRID 473728 reaction equation
F[C:2]1[C:3]([CH:8]2[CH2:12][CH2:11][N:10]([C:13](=[O:15])[CH3:14])[CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.[N:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[NH:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[N:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[NH:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][C:2]2[C:3]([CH:8]3[CH2:12][CH2:11][N:10]([C:13](=[O:15])[CH3:14])[CH2:9]3)=[N:4][CH:5]=[CH:6][N:7]=2)=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 212625714-(Pyridin-2-ylamino)phenolHCID 59373920HCID 59373920, compound

Product 1

HCID 59373995HCID 59373995, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

A glass microwave reaction vessel was charged with 1-(3-(3-fluoropyrazin-2-yl)pyrrolidin-1-yl)ethanone (78 mg, 0.37 mmol), 4-(pyridin-2-ylamino)phenol (139 mg, 0.746 mmol), cesium carbonate (243 mg, 0.746 mmol), and DMSO (1.2 mL). The reaction mixture was degassed and flushed with N2 and heated in an oil bath at 80° C. for 20 h. After cooling to RT, the reaction mixture was partitioned between EtOAc and 1 N NH4Cl. The aqueous layer was back extracted with EtOAc (2×) and the combined organic layer was washed with water, brine, dried (Na2SO4) and concentrated. The crude material was chromatographed through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 100% EtOAc in hexane, then 5% MeOH in EtOAc, to provide 1-(3-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)pyrrolidin-1-yl)ethanone as an off-white solid. MS (ESI, pos. ion) m/z: 376.1 (M+1). IC50 (uM) 0.0164.

Workup

  1. customA glass microwave reaction vessel
  2. customThe reaction mixture was degassed
  3. customflushed with N2
  4. temperatureAfter cooling to RT
  5. customthe reaction mixture was partitioned between EtOAc and 1 N NH4Cl
  6. extractionThe aqueous layer was back extracted with EtOAc (2×)
  7. washthe combined organic layer was washed with water, brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customThe crude material was chromatographed through a Redi-Sep pre-packed silica gel column (40 g)
  11. washeluting with a gradient of 0% to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-16abe74f924f47648144f838f26eb0fe
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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