Potassium Carbonate → {5-[1-Biphenyl-4-ylmethyl-6-chloro-5-(1-methyl-1H-indol-5-yl)-1H-benzoimidazol-2-yloxy]-2-methyl-phenyl}-phosphonic acid diethyl ester

HRID 1960152Notes

Reaction equation

HRID 1960152 reaction equation
[CH2:1]([O:3][P:4]([C:9]1[CH:14]=[C:13]([O:15][C:16]2[N:20]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:24][CH:23]=3)[C:19]3[CH:34]=[C:35]([Cl:39])[C:36](I)=[CH:37][C:18]=3[N:17]=2)[CH:12]=[CH:11][C:10]=1[CH3:40])(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[CH3:41][N:42]1[C:50]2[C:45](=[CH:46][C:47](B(O)O)=[CH:48][CH:49]=2)[CH:44]=[CH:43]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([O:3][P:4]([C:9]1[CH:14]=[C:13]([O:15][C:16]2[N:20]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:24][CH:23]=3)[C:19]3[CH:34]=[C:35]([Cl:39])[C:36]([C:47]4[CH:46]=[C:45]5[C:50](=[CH:49][CH:48]=4)[N:42]([CH3:41])[CH:43]=[CH:44]5)=[CH:37][C:18]=3[N:17]=2)[CH:12]=[CH:11][C:10]=1[CH3:40])(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27598671-Methyl-1H-indole-5-boronic acidHCID 86761791[5-(1-Biphenyl-4-ylmethyl-6-chloro-5-iodo-1H-benzoimidazol-2-yloxy)-2-methyl-phenyl]-phosphonic acid diethyl ester

Product 1

HCID 86761792{5-[1-Biphenyl-4-ylmethyl-6-chloro-5-(1-methyl-1H-indol-5-yl)-1H-benzoimidazol-2-yloxy]-2-methyl-phenyl}-phosphonic acid diethyl ester

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of {5-[1-biphenyl-4-ylmethyl-6-chloro-5-Iodo-1H-benzoimidazol-2-yloxy]-2-methyl-phenyl}-phosphonic acid diethyl ester (900 mg, 1.3 mmol) in DMF (6 ml) was added 1-methyl-1H-indole-5-boronic acid (460 mg, 2.6 mmol), tetrakis(triphenylphosphine)-palladium(0) (155 mg, 0.13 mmol), and lastly a solution of potassium carbonate (718 mg, 5.2 mmol) in 3 ml of H2O. The mixture was heated in a microwave oven at 130° C. for 15 min. The reaction was partitioned between EtOAc and half-saturated NH4Cl. The EtOAc layer was washed with H2O and then brine. The organic layer was dried with MgSO4, evaporated to an oil, and then purified by flash chromatography. The flash column was eluted with a solvent gradient up to 65% EtOAc in Hexane to isolate the title compound as a mixture of the two protected regioisomers.

Workup

  1. customThe reaction was partitioned between EtOAc and half-saturated NH4Cl
  2. washThe EtOAc layer was washed with H2O
  3. dry with materialThe organic layer was dried with MgSO4
  4. customevaporated to an oil
  5. custompurified by flash chromatography
  6. washThe flash column was eluted with a solvent gradient up to 65% EtOAc in Hexane

Sources & evidence

ORD record
ord-6ecc2038f5634ecaabb807aa142c9e79
Source dataset
uspto-grants-2013_04
Patent number
US08410284B2

Reaction notes

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