Propargyl alcohol → 4-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide

HRID 917697Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 917697
[F:1][C:2]1[CH:23]=[C:22](I)[CH:21]=[CH:20][C:3]=1[NH:4][C:5]1[C:6]([C:13]([NH:15][O:16][CH2:17][CH2:18][OH:19])=[O:14])=[CH:7][N:8]([CH3:12])[C:9](=[O:11])[CH:10]=1.[CH2:25]([OH:28])[C:26]#[CH:27]>[Cu]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.C1COCC1>[F:1][C:2]1[CH:23]=[C:22]([C:27]#[C:26][CH2:25][OH:28])[CH:21]=[CH:20][C:3]=1[NH:4][C:5]1[C:6]([C:13]([NH:15][O:16][CH2:17][CH2:18][OH:19])=[O:14])=[CH:7][N:8]([CH3:12])[C:9](=[O:11])[CH:10]=1

Komponenten

6

Edukt 2

HCID 7859Propargyl alcoholHCID 112130144-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide

Produkt 1

HCID 111996954-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

4-(2-Fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide (330 mg, 0.74 mmol), CuI (3 mg, 0.01 mmol) and (Ph3P)2PdCl2 (104 mg, 0.01 mmol) were dissolved dry THF (2 mL) in a flask which was then flushed with nitrogen. A solution of propargyl alcohol (47 mg, 0.81 mmol) in TEA (2 mL) was added to the reaction, which was stirred at R.T. for 15 h. The solvent was removed under reduced pressure, then the residue purified by chromatography on silica gel (10% MeOH/CH2Cl2 as eluant), giving 4-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide as a viscous, transparent oil (44%). 1H NMR [(CD3)2SO, 400 MHz] δ 11.50 (v br s, 1H), 9.60 (s, 1H), 8.16 (s, 1H), 7.49 (t, J=8.3 Hz, 1H), 7.40 (dd, J=10.1, 1.9 Hz, 1H), 7.28 (dd, J=8.3, 1.4 Hz, 1H), 5.67 (s, 1H), 5.37 (t, J=5.1 Hz, 1H), 4.73 (br s, 1H), 4.30 (d, J=4.8 Hz, 2H), 3.91 (t, J=4.8 Hz, 2H), 3.62 (br t, J=4.8 Hz, 2H), 3.36 (s, 3H). LCMS (APCI+) calcd for C18H19N3O5F 376 (MH+), found 376.

Aufarbeitung

  1. customwas then flushed with nitrogen
  2. customThe solvent was removed under reduced pressure
  3. customthe residue purified by chromatography on silica gel (10% MeOH/CH2Cl2 as eluant)

Quellen und Nachweise

ORD-Eintrag
ord-09b9b34c57a54d8aa49e804fb45bc6a6
Quelldatensatz
uspto-grants-2007_09
Patentnummer
US07273877B2

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