Cesium carbonate → 4-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)cycloheptanone

HRID 410252Notes

Reaction equation

HRID 410252 reaction equation
[C:1](=[O:4])([O-])[O-].[Cs+].[Cs+].[NH:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[C:16]([C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1)=[O:17].F[C:26]1[C:31]([CH:32]2[CH2:38][CH2:37]N[C:35](=O)[CH2:34][CH2:33]2)=[CH:30][CH:29]=[CH:28][N:27]=1>CN1C(=O)CCC1>[NH:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[C:16]([C:18]1[CH:23]=[CH:22][C:21]([O:24][C:26]2[C:31]([CH:32]3[CH2:33][CH2:34][CH2:35][C:1](=[O:4])[CH2:37][CH2:38]3)=[CH:30][CH:29]=[CH:28][N:27]=2)=[CH:20][CH:19]=1)=[O:17]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 593268345-(2-Fluoropyridin-3-yl)azepan-2-oneHCID 59326874(1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanone

Product 1

HCID 593269804-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)cycloheptanone

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of cesium carbonate (0.24 g, 0.72 mmol), (1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanone (0.17 g, 0.72 mmol), and 5-(2-fluoropyridin-3-yl)azepan-2-one (0.050 g, 0.24 mmol) in NMP (0.25 mL) under argon was heated to 140° C. for 36 h. After cooling to room temperature, the mixture was partitioned between ethyl acetate and water. The layers were separated and the organic layer was washed with water several times, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The resulting oil was purified by reversed phase HPLC, and the resulting oil was dissolved in DCM and washed with saturated aqueous sodium bicarbonate (2×), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give 4-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)cycloheptanone. MS (ESI, pos. ion) m/z: 427.1 (M+1). IC50 (uM) +++++.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was partitioned between ethyl acetate and water
  3. customThe layers were separated
  4. washthe organic layer was washed with water several times
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting oil was purified by reversed phase HPLC
  9. dissolutionthe resulting oil was dissolved in DCM
  10. washwashed with saturated aqueous sodium bicarbonate (2×)
  11. dry with materialdried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d47a6879f4144f0495c642ed1c7d3cfc
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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