Cesium carbonate → 2-(4-(1-methyl-1H-benzo[d]imidazol-2-ylamino)phenoxy)nicotinonitrile

HRID 410187Notes

Reaction equation

HRID 410187 reaction equation
[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Cs+].[Cs+].F[C:26]1[N:33]=[CH:32][CH:31]=[CH:30][C:27]=1[C:28]#[N:29]>CS(C)=O.CCOC(C)=O>[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]=[C:3]1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][C:26]2[N:33]=[CH:32][CH:31]=[CH:30][C:27]=2[C:28]#[N:29])=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27832543-Cyano-2-fluoropyridineHCID 593270144-(1-methyl-1H-benzoimidazol-2-ylamino)-phenol

Product 1

HCID 593271972-(4-(1-methyl-1H-benzo[d]imidazol-2-ylamino)phenoxy)nicotinonitrile

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-(1-methyl-1H-benzo[d]imidazol-2-ylamino)phenol (120 mg, 0.5 mmol) in DMSO (1 mL) was added cesium carbonate (196 mg, 0.6 mmol) and 2-fluoronicotinonitrile (61 mg, 0.5 mmol). The resulting mixture was heated to 80° C. for 16 h. After cooling to RT, the reaction mixture was diluted with EtOAc and washed with water and brine several times to remove DMSO. The aqueous layer was back extracted with EtOAc (3×) and the combined organic layer was dried (Na2SO4) and concentrated. The crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 0% to 5% of MeOH in CH2Cl2, followed by trituration with ether, to provide 2-(4-(1-methyl-1H-benzo[d]imidazol-2-ylamino)phenoxy)nicotinonitrile as off-white solid. MS (ESI, pos. ion) m/z: 342.2 (M+1). IC50 (uM) +++++.

Workup

  1. temperatureAfter cooling to RT
  2. washwashed with water and brine several times
  3. customto remove DMSO
  4. extractionThe aqueous layer was back extracted with EtOAc (3×)
  5. dry with materialthe combined organic layer was dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe crude product was chromatographed through a Redi-Sep® pre-packed silica gel column (40 g)
  8. washeluting with a gradient of 0% to 5% of MeOH in CH2Cl2

Sources & evidence

ORD record
ord-39b4b9cfc4b44c0e8bd30f1e7835c411
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

Loading…