Potassium Carbonate → (E)-2-(2,6-dichlorobenzamido)-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester

HRID 1752086Notes

Reaction equation

HRID 1752086 reaction equation
CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH3:23][O:24][C:25](=[O:41])[CH:26]([NH:30][C:31](=[O:40])[C:32]1[C:37]([Cl:38])=[CH:36][CH:35]=[CH:34][C:33]=1[Cl:39])[CH2:27][CH:28]=[CH2:29].I[C:43]1[CH:48]=[CH:47][C:46]([N:49]([CH3:56])[C:50]2[N:55]=[CH:54][CH:53]=[CH:52][N:51]=2)=[CH:45][CH:44]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[CH3:23][O:24][C:25](=[O:41])[CH:26]([NH:30][C:31](=[O:40])[C:32]1[C:33]([Cl:39])=[CH:34][CH:35]=[CH:36][C:37]=1[Cl:38])[CH2:27]/[CH:28]=[CH:29]/[C:43]1[CH:48]=[CH:47][C:46]([N:49]([CH3:56])[C:50]2[N:51]=[CH:52][CH:53]=[CH:54][N:55]=2)=[CH:45][CH:44]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 80271Tri-o-tolylphosphineHCID 46184395N-(4-iodophenyl)-N-methylpyrimidin-2-amineHCID 577625182-(2,6-Dichlorobenzamido)pent-4-enoic acid methyl ester

Product 1

HCID 57762525(E)-2-(2,6-dichlorobenzamido)-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl esterYield 67.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Under an argon atmosphere, palladium acetate (170.8 mg) and tris(2-methylphenyl)phosphine (222.2 mg) were added to a suspension of 2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl ester (2.20 g), N-(4-iodophenyl)-N-methylpyrimidin-2-amine (2.27 g) and potassium carbonate (1.51 g) in DMF (20 ml), and the resulting mixture was stirred at 80° C. for 3 hours. After cooling the reaction solution to room temperature, ethyl acetate was added to the reaction solution, and the resulting mixture was washed twice with water and once with saturated brine, followed by drying the organic layer 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=1/1→chloroform). The obtained crude product was purified again by column chromatography (silica gel, eluent: cyclohexane/ethyl acetate=4/1→2/1) to obtain (E)-2-(2,6-dichlorobenzamido)-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester (2.38 g).

Workup

  1. temperatureAfter cooling the reaction solution to room temperature
  2. washthe resulting mixture was washed twice with water and once with saturated brine
  3. dry with materialby drying the organic layer over anhydrous sodium sulfate
  4. customAfter removing anhydrous sodium sulfate
  5. filtrationby filtration
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by column chromatography (silica gel, eluent: cyclohexane/chloroform=1/1→chloroform)
  8. customThe obtained crude product
  9. customwas purified again by column chromatography (silica gel, eluent: cyclohexane/ethyl acetate=4/1→2/1)

Sources & evidence

ORD record
ord-4105215b807a4b94a134dcb8586a9e7f
Source dataset
uspto-grants-2015_10
Patent number
US09162988B2

Reaction notes

Loading…