Benzo(B)Thiophene-2-Boronic Acid → 2-(1-Benzothien-2-yl)-5-[(2-phenylbutanoyl)amino]benzamide

HRID 503693Notes

Reaction equation

HRID 503693 reaction equation
I[C:2]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:22])[CH:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:14][CH3:15])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[S:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[CH:25]=[C:24]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[S:23]1[C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[CH:25]=[C:24]1[C:2]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:22])[CH:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:14][CH3:15])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5]

Participants

6

Reactant 3

HCID 2359Benzo(B)Thiophene-2-Boronic AcidHCID 10340Sodium CarbonateHCID 594284852-Iodo-5-[(2-phenylbutanoyl)amino]benzamide

Product 1

HCID 115897092-(1-Benzothien-2-yl)-5-[(2-phenylbutanoyl)amino]benzamide

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 500 mg (1.23 mmol) of the compound of Example 5A, 262 mg (1.47 mmol) of 1-benzothien-2-ylboronic acid, 1.34 ml (2.70 mmol, 2M solution in water) of sodium carbonate and 42 mg (0.061 mmol) of bis(triphenylphosphine)palladium(II) chloride in 10 ml of dimethoxyethane are stirred under reflux for 3 hours. The solution is cooled to room temperature and then partitioned between 500 ml of ethyl acetate and water, and the aqueous phase is extracted twice with 200 ml of ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered with suction and concentrated. The residue is dissolved in dimethyl sulfoxide and purified by preparative RP-HPLC with acetonitrile and water. 146 mg (29% of theory) of the title compound are obtained.

Workup

  1. temperatureunder reflux for 3 hours
  2. custompartitioned between 500 ml of ethyl acetate and water
  3. extractionthe aqueous phase is extracted twice with 200 ml of ethyl acetate
  4. washThe combined organic phases are washed with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered with suction
  7. concentrationconcentrated
  8. dissolutionThe residue is dissolved in dimethyl sulfoxide
  9. custompurified by preparative RP-HPLC with acetonitrile and water

Sources & evidence

ORD record
ord-4fee28b43d094588a14d4a44e3951a8a
Source dataset
uspto-grants-2010_08
Patent number
US07776922B2

Reaction notes

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