2,5-Dihydrofuran → (1H-benzo[d]imidazol-2-yl)(4-(3-(2,3-dihydro furan-3-yl)pyridin-2-yloxy)phenyl)methanone

HRID 1880157Notes

Reaction equation

HRID 1880157 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](Br)=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:14][CH:13]=1)=[O:11].[O:26]1[CH2:30][CH:29]=[CH:28][CH2:27]1.C1(N(C)C2CCCCC2)CCCCC1>O1CCOCC1.CCOC(C)=O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[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]([CH:30]3[CH2:29][CH:28]=[CH:27][O:26]3)=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:14][CH:13]=1)=[O:11].[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]([CH:29]3[CH:28]=[CH:27][O:26][CH2:30]3)=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:14][CH:13]=1)=[O:11]

Participants

8

Reactant 3

HCID 155702,5-DihydrofuranHCID 24210N-Methyl dicyclohexylamineHCID 59326957(1H-benzo[d]imidazol-2-yl)(4-(3-bromopyridin-2-yloxy)phenyl)methanone

Product 2

HCID 59326803(1H-benzo[d]imidazol-2-yl)(4-(3-(2,3-dihydro furan-3-yl)pyridin-2-yloxy)phenyl)methanoneHCID 59327153(1H-benzo[d]imidazol-2-yl)(4-(3-(2,3-dihydrofuran-2-yl)pyridin-2-yloxy)phenyl)methanone

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (1H-benzo[d]imidazol-2-yl)(4-(3-bromopyridin-2-yloxy)phenyl)methanone (1.522 g, 3.86 mmol), 2,5-dihydrofuran (1.400 mL, 18.98 mmol, Aldrich), N-cyclohexyl-N-methylcyclohexanamine (1.600 mL, 7.54 mmol, Aldrich) and bis(tri-tert-butylphosphine)palladium (0) (0.194 g, 0.380 mmol, Strem) in dioxane (10 mL) was sealed in a microwave vessel under an atmosphere of argon and heated thermally at 80° C. for 6 h. The reaction was diluted with EtOAc and the mixture was extracted with water (1×) and brine (1×). The organic mixture was evaporated onto silica gel and purified by flash chromatography (Isco (120 gram)) eluting with EtOAc:hexanes (0:1→1:2) to give 650 mg of (1H-benzo[d]imidazol-2-yl)(4-(3-(2,3-dihydrofuran-2-yl)pyridin-2-yloxy)phenyl)methanone and 325 mg of (1H-benzo[d]imidazol-2-yl)(4-(3-(2,3-dihydro furan-3-yl)pyridin-2-yloxy)phenyl)methanone.

Workup

  1. customwas sealed in a microwave vessel under an atmosphere of argon
  2. extractionthe mixture was extracted with water (1×) and brine (1×)
  3. customThe organic mixture was evaporated onto silica gel
  4. custompurified by flash chromatography (Isco (120 gram))
  5. washeluting with EtOAc:hexanes (0:1→1:2)

Sources & evidence

ORD record
ord-a535a073c682409d9bf103a67e3fdae0
Source dataset
uspto-grants-2012_11
Patent number
US08318718B2

Reaction notes

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