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

HRID 1752096

Reaktionsgleichung

Reaktionsgleichung von HRID 1752096
CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH3:23][O:24][C:25](=[O:41])[C@@H: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])[C@@H: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

Komponenten

8

Edukt 4

HCID 11430Potassium CarbonateHCID 80271Tri-o-tolylphosphineHCID 46184395HCID 46184395, VerbindungHCID 57762562(S)-2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl ester

Produkt 1

HCID 57762554(S,E)-2-(2,6-dichlorobenzamido)-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl esterAusbeute 66,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Under an argon atmosphere, palladium acetate (93.2 mg) and tris(2-methylphenyl)phosphine (121.2 mg) were added to a suspension of (S)-2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl ester (1.20 g), N-(4-iodophenyl)-N-methylpyrimidin-2-amine (1.24 g) and potassium carbonate (824 mg) 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 thereto, 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 (S,E)-2-(2,6-dichlorobenzamido)-5-[4-(methyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester (1.28 g).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-5f6c13ca7fe44051b79e0c52f632b99a
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09162988B2

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