Dichloromethane → {4-[(Pyrid-3-yl)ethynyl]-2-phenylbenzoyl]methionine methyl ester

HRID 2121191Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2121191
[CH3:1][O:2][C:3](=[O:25])[C@H:4]([CH2:21][CH2:22][S:23][CH3:24])[NH:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10](I)=[CH:9][C:8]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.ClCCl.[C:29]([Sn](CCCC)(CCCC)CCCC)#[CH:30].[I-].Br[C:46]1[CH:47]=[N:48][CH:49]=[CH:50][CH:51]=1.C(N(CC)CC)C>CN(C=O)C.CCOCC.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3](=[O:25])[C@H:4]([CH2:21][CH2:22][S:23][CH3:24])[NH:5][C:6](=[O:20])[C:7]1[CH:12]=[CH:11][C:10]([C:29]#[C:30][C:46]2[CH:47]=[N:48][CH:49]=[CH:50][CH:51]=2)=[CH:9][C:8]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Komponenten

11

Edukt 6

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 122863-BromopyridineHCID 30165Iodide IonHCID 621176EthynyltributyltinHCID 53801632(4-Iodo-2-phenylbenzoyl)methionine methyl ester

Produkt 1

HCID 20622839{4-[(Pyrid-3-yl)ethynyl]-2-phenylbenzoyl]methionine methyl esterAusbeute 24 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of (4-iodo-2-phenylbenzoyl)methionine methyl ester, prepared as in Example 210D, (469 mg, 1.0 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride, complexed to dichloromethane (1:1) (82 mg, 0.10 mmol), and ethynyltributyltin (315 mg, 1.0 mmol) in DMF (5 mL) was heated at 80° C. for 6 hours at which point thin layer chromatography indicated no starting iodide left. 3-Bromopyridine (0.114 mL, 1.2 mmol) and triethylamine (0.42 mL, 3.0 mmol) were added and the reaction mixture was heated at 100° C. for 14 hours. The reaction mixture was diluted with ether (50 mL) and ethyl acetate (50 mL), washed with water and brine, dried over anhydrous magnesium sulfate, and filtered. To the filtrate was added 3 drops of water, followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (0.2 mL) with swirling. The resulting milky mixture was filtered through silica gel (15 g), rinsed with ethyl acetate, and concentrated in vacuo. The residue was then purified by column chromatography (50% ethyl acetate-hexane, then ethyl acetate) to give {4-[(pyrid-3-yl)ethynyl]-2-phenylbenzoyl}methionine methyl ester (109 mg, 24%). 1H NMR (300 MHz, CDCl3) δ 8.79 (s, 1H), 8.58 (dd, 1H), 7.82 (dt, 1H), 7.74 (d, 1H), 7.59 (dd, 1H), 7.57 (s, 1H), 7.45 (m, 5H), 7.31 (dd, 1H), 5.93 (br d, 1H), 4.69 (m, 1H), 3.68 (s, 3H), 2.08 (m, 2H), 2.02 (s, 3H), 1.93 (m, 1H), 1.76 (m, 1H). MS (CI+) m/e 445 (M+H)+.

Aufarbeitung

  1. waitleft
  2. temperaturethe reaction mixture was heated at 100° C. for 14 hours
  3. washwashed with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. additionTo the filtrate was added 3 drops of water
  7. filtrationThe resulting milky mixture was filtered through silica gel (15 g)
  8. washrinsed with ethyl acetate
  9. concentrationconcentrated in vacuo
  10. customThe residue was then purified by column chromatography (50% ethyl acetate-hexane

Quellen und Nachweise

ORD-Eintrag
ord-f581f5f8742d4882aecd016f46288241
Quelldatensatz
uspto-grants-2004_02
Patentnummer
US06693123B2

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