Cesium carbonate → (1H-benzo[d]imidazol-2-yl)(4-(3-(tetrahydro-2H-pyran-3-yl)pyridin-2-yloxy)phenyl)methanone

HRID 410230Notes

Reaction equation

HRID 410230 reaction equation
F[C:2]1[C:7]([CH:8]2[CH2:13][CH2:12][CH2:11][O:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=[C:15]1[C:23]([C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=1)=[O:24].C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.O>[NH:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=[C:15]1[C:23]([C:25]1[CH:30]=[CH:29][C:28]([O:31][C:2]2[C:7]([CH:8]3[CH2:13][CH2:12][CH2:11][O:10][CH2:9]3)=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:27][CH:26]=1)=[O:24]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 59326874(1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanoneHCID 593269202-fluoro-3-(tetrahydro-2H-pyran-3-yl)pyridine

Product 1

HCID 59326862(1H-benzo[d]imidazol-2-yl)(4-(3-(tetrahydro-2H-pyran-3-yl)pyridin-2-yloxy)phenyl)methanone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

2-Fluoro-3-(tetrahydro-2H-pyran-3-yl)pyridine (0.10 g, 0.55 mmol), (1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanone (0.33 g, 1.38 mmol), and cesium carbonate (0.54 g, 1.66 mmol) were mixed in NMP (2 mL). The reaction mixture was placed under a nitrogen atmosphere and stirred at 140° C. for 72 h. The reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc (2×). The combined organic layers were washed with 1 M aqueous sodium hydroxide (1×), sat. sodium chloride (1×), dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel chromatography to give (1H-benzo[d]imidazol-2-yl)(4-(3-(tetrahydro-2H-pyran-3-yl)pyridin-2-yloxy)phenyl)methanone. MS (ESI, pos. ion) m/z: 400.1 (M+1). IC50 (uM) +++++.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic layers were washed with 1 M aqueous sodium hydroxide (1×), sat. sodium chloride (1×)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-cb1d492b91c247bfa5bc7b20291a5780
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

Loading…