Cesium carbonate → Amg 579

HRID 555883Notes

Reaction equation

HRID 555883 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)=[O:11].F[C:20]1[C:21]([CH:26]2[CH2:31][CH2:30][N:29]([C:32](=[O:34])[CH3:33])[CH2:28][CH2:27]2)=[N:22][CH:23]=[CH:24][N:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][C:15]([O:18][C:20]2[C:21]([CH:26]3[CH2:27][CH2:28][N:29]([C:32](=[O:34])[CH3:33])[CH2:30][CH2:31]3)=[N:22][CH:23]=[CH:24][N:25]=2)=[CH:14][CH:13]=1)=[O:11]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 59326874(1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanoneHCID 593512871-(4-(3-Fluoropyrazin-2-yl)piperidin-1-yl)ethanone

Product 1

HCID 59351313Amg 579

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

The mixture of (1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanone (0.16 g, 0.67 mmol), 1-(4-(3-fluoropyrazin-2-yl)piperidin-1-yl)ethanone (0.1 g, 0.45 mmol), and cesium carbonate (0.22 g, 0.67 mmol) in DMSO (1.5 mL) was heated at 80° C. for 20 h. After cooling to RT, the reaction mixture was partitioned between Teac and brine. The aqueous layer was back extracted with Teac (2×) and the combined organic layer was dried (Na2SO4) and concentrated. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 100% Teac in hexane, then 5% MeOH in Teac, to provide 1-(4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone as off-white solid. MS (ESI, pos. ion) m/z: 442.1 (M+1). IC50 (uM) +++++.

Workup

  1. temperatureAfter cooling to RT
  2. customthe reaction mixture was partitioned between Teac and brine
  3. extractionThe aqueous layer was back extracted with Teac (2×)
  4. dry with materialthe combined organic layer was dried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  7. washeluting with a gradient of 0% to 100% Teac in hexane

Sources & evidence

ORD record
ord-7f21740342ec4dbf9a59d1d12988842d
Source dataset
uspto-grants-2011_11
Patent number
US08053438B2

Reaction notes

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