HCID 59351292, compound → HCID 178519710, compound

HRID 887420Notes

Reaction equation

HRID 887420 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]([O:18][C:19]2[C:24]([C:25]3[CH2:30][CH2:29][CH:28]([OH:31])[CH2:27][CH:26]=3)=[N:23][CH:22]=[CH:21][N:20]=2)=[CH:14][CH:13]=1)=[O:11]>CCOC(C)=O.[Pd].[O-2].[O-2].[Mn+4]>[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:19]2[C:24]([C@H:25]3[CH2:30][CH2:29][C@@H:28]([OH:31])[CH2:27][CH2:26]3)=[N:23][CH:22]=[CH:21][N:20]=2)=[CH:14][CH:13]=1)=[O:11]

Participants

5

Reactant 1

HCID 59351292HCID 59351292, compound

Product 1

HCID 178519710HCID 178519710, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 178418406HCID 178418406, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

1H-benzimidazol-2-yl(4-((3-(4-hydroxy-1-cyclohexen-1-yl)-2-pyrazinyl)oxy)-phenyl)methanone (0.27 g, 0.66 mmol) was suspended in 20 mL of EtOAc in a pressure tube. Palladium on carbon, 10% (0.20 g) was added. The mixture was hydrogenated at 50 psi. After 60 hours the mixture was filtered through a plug of celite and eluted with 50 mL of 9:1 chloroform:isopropanol. The solvent was removed under reduced pressure. The residue was taken up in 50 mL of dichloromethane. The mixture was sonicated for 5 minutes to dissolve the starting material. Manganese dioxide (0.84 g, 9.7 mmol) was added. After 2 hours, the mixture was filtered through celite, eluted with 50 mL of 9:1 chloroform/isopropanol, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (0 to 2.5% MeOH/dichloromethane). Two products of identical mass that co-eluted were isolated. The mixture was further purified by preparatory HPLC (Phenomenex Gemini column [C18, 10 micro, 150×30 mm] 15% to 100% MeCN/water over 20 min at 35 mL/min) affording 1H-benzimidazol-2-yl(4-((3-(cis-4-hydroxycyclohexyl)-2-pyrazinyl)oxy)phenyl)methanone (MS m/z: 401 (M+1) and 1H-benzimidazol-2-yl(4-((3-(trans-4-hydroxycyclohexyl)-2-pyrazinyl)oxy)-phenyl)methanone. MS (ESI, pos. ion) m/z: 401 (M+1). IC50 (uM) +++++.

Workup

  1. filtrationAfter 60 hours the mixture was filtered through a plug of celite
  2. washeluted with 50 mL of 9:1 chloroform
  3. customThe solvent was removed under reduced pressure
  4. customThe mixture was sonicated for 5 minutes
  5. dissolutionto dissolve the starting material
  6. filtrationthe mixture was filtered through celite
  7. washeluted with 50 mL of 9:1 chloroform/isopropanol
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel (0 to 2.5% MeOH/dichloromethane)
  10. customTwo products of identical mass that co-eluted were isolated
  11. customThe mixture was further purified by preparatory HPLC (Phenomenex Gemini column [C18, 10 micro, 150×30 mm] 15% to 100% MeCN/water over 20 min at 35 mL/min)

Sources & evidence

ORD record
ord-746c0603a13e4e4099f1ccd0b67c582b
Source dataset
uspto-grants-2012_08
Patent number
US08247418B2

Reaction notes

Loading…