2-(4-Iodophenoxy)pyrimidine → 2-(2,6-Dichlorobenzamido)-5-[4-(pyrimidin-2-yloxy)phenyl]pent-4-ynoic acid methyl ester

HRID 1360082

Reaction equation

HRID 1360082 reaction equation
[CH3:1][O:2][C:3](=[O:19])[CH:4]([NH:8][C:9](=[O:18])[C:10]1[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:17])[CH2:5][C:6]#[CH:7].I[C:21]1[CH:33]=[CH:32][C:24]([O:25][C:26]2[N:31]=[CH:30][CH:29]=[CH:28][N:27]=2)=[CH:23][CH:22]=1>C1COCC1.C(NC(C)C)(C)C.[Cu](I)I.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>[CH3:1][O:2][C:3](=[O:19])[CH:4]([NH:8][C:9](=[O:18])[C:10]1[C:11]([Cl:17])=[CH:12][CH:13]=[CH:14][C:15]=1[Cl:16])[CH2:5][C:6]#[C:7][C:21]1[CH:33]=[CH:32][C:24]([O:25][C:26]2[N:27]=[CH:28][CH:29]=[CH:30][N:31]=2)=[CH:23][CH:22]=1

Participants

6

Reactant 2

HCID 14846172-(4-Iodophenoxy)pyrimidineHCID 206102962-(2,6-Dichlorobenzamido)pent-4-ynoic acid methyl ester

Product 1

HCID 577624772-(2,6-Dichlorobenzamido)-5-[4-(pyrimidin-2-yloxy)phenyl]pent-4-ynoic acid methyl esterYield 86.2%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 18968793THF diisopropylamineSolvent

Procedure

Under an argon atmosphere, copper iodide (2.8 mg) and dichlorobis(triphenylphosphine)palladium (5.2 mg) were added to a solution of 2-(2,6-dichlorobenzamido)pent-4-ynoic acid methyl ester (74 mg) and 2-(4-iodophenoxy)pyrimidine (81 mg) in THF/diisopropylamine (3/1) mixture (5 ml), and the resulting mixture was stirred at room temperature for 2 hours. The reaction solution was concentrated and ethyl acetate was added to the residue. The insoluble matter was removed by filtration, and the filtrate was washed once with water and once with saturated brine and dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated. The residue was purified by column chromatography (silica gel, eluent:cyclohexane/chloroform=2/1→cyclohexane/chloroform=1/3) to obtain 2-(2,6-dichlorobenzamido)-5-[4-(pyrimidin-2-yloxy)phenyl]pent-4-ynoic acid methyl ester (100 mg).

Workup

  1. concentrationThe reaction solution was concentrated
  2. additionethyl acetate was added to the residue
  3. customThe insoluble matter was removed by filtration
  4. washthe filtrate was washed once with water and once with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customAfter removing anhydrous sodium sulfate
  7. filtrationby filtration
  8. concentrationthe filtrate was concentrated
  9. customThe residue was purified by column chromatography (silica gel, eluent:cyclohexane/chloroform=2/1→cyclohexane/chloroform=1/3)

Sources & evidence

ORD record
ord-f82ca55abb204406a1aeb7efa9215e81
Source dataset
uspto-grants-2011_02
Patent number
US07879837B2

Linked notes

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