Imidazole → 1-{3-Fluoro-4-[4-(5-imidazol-1-yl-2-morpholin-4-yl-benzoyl)-piperazin-1-yl]-phenyl}-ethanone

HRID 32728

Reaction equation

HRID 32728 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)=[C:6]([CH:25]=1)[C:7]([N:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:23])[CH3:22])=[CH:17][C:16]=2[F:24])[CH2:11][CH2:10]1)=[O:8].[NH:32]1[CH:36]=[CH:35][N:34]=[CH:33]1.C(=O)([O-])[O-].[Cs+].[Cs+].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1>[Cu]I.O1CCOCC1>[F:24][C:16]1[CH:17]=[C:18]([C:21](=[O:23])[CH3:22])[CH:19]=[CH:20][C:15]=1[N:12]1[CH2:13][CH2:14][N:9]([C:7](=[O:8])[C:6]2[CH:25]=[C:2]([N:32]3[CH:36]=[CH:35][N:34]=[CH:33]3)[CH:3]=[CH:4][C:5]=2[N:26]2[CH2:27][CH2:28][O:29][CH2:30][CH2:31]2)[CH2:10][CH2:11]1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 13181,10-PhenanthrolineHCID 10796Cesium carbonateHCID 445805131-(4-(4-(5-Bromo-2-morpholinobenzoyl)piperazin-1-yl)-3-fluorophenyl)ethanone

Product 1

HCID 597936961-{3-Fluoro-4-[4-(5-imidazol-1-yl-2-morpholin-4-yl-benzoyl)-piperazin-1-yl]-phenyl}-ethanoneYield 41.9%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

In a tube were added successively 1-{4-[4-(5-Bromo-2-morpholin-4-yl-benzoyl)-piperazin-1-yl]-3-fluoro-phenyl}-ethanone (example BJ, 0.05 g, 0.1 mmol), imidazole (8.4 mg, 0.12 mmol), cesium carbonate (70 mg, 0.21 mmol), CuI (4 mg, 0.02 mmol), 1,10-phenanthroline (7.3 mg, 0.04 mmol) and dioxane (0.2 ml). The mixture was heated under argon at 120° C. for 12 hours. The reaction mixture was cooled to room temperature and quenched with water/ethyl acetate. The aqueous layer was extracted twice with ethylacetate. The organic layers were combined, dried over Na2SO4, filtered and the solvent was removed in vacuo. The crude oil was chromatographed over silicagel: eluent: CH2Cl2/methanol: 0-5% to provide the title compound as a brown solid (20 mg, 40%), MS (m/e): 478.4 (M+H, 100%)

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched with water/ethyl acetate
  3. extractionThe aqueous layer was extracted twice with ethylacetate
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. customThe crude oil was chromatographed over silicagel

Sources & evidence

ORD record
ord-a4c32b96617f474fb32d70c7f6e317c6
Source dataset
uspto-grants-2008_09
Patent number
US07427612B2

Linked notes

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