Triethylamine → N-Isopropyl-1-[3-(3-hydroxy-3-phenylbut-1-ynyl)phenyl]-1,4-dihydro [1,8]naphthyridin-4-one-3-carboxamide

HRID 351735

Reaktionsgleichung

Reaktionsgleichung von HRID 351735
[CH:1]([NH:4][C:5]([C:7]1[C:16](=[O:17])[C:15]2[C:10](=[N:11][CH:12]=[CH:13][CH:14]=2)[N:9]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20](Br)[CH:19]=2)[CH:8]=1)=[O:6])([CH3:3])[CH3:2].[C:25]1([C:31]([OH:35])([C:33]#[CH:34])[CH3:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(CC)CC)C>CN(C=O)C.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl.[Cu]I>[CH:1]([NH:4][C:5]([C:7]1[C:16](=[O:17])[C:15]2[C:10](=[N:11][CH:12]=[CH:13][CH:14]=2)[N:9]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:34]#[C:33][C:31]([OH:35])([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH3:32])[CH:19]=2)[CH:8]=1)=[O:6])([CH3:3])[CH3:2]

Komponenten

8

Edukt 3

HCID 8471TriethylamineHCID 920983-Hydroxy-3-phenyl-1-butyneHCID 129913181-(3-bromophenyl)-N-isopropyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide

Produkt 1

HCID 10161154N-Isopropyl-1-[3-(3-hydroxy-3-phenylbut-1-ynyl)phenyl]-1,4-dihydro [1,8]naphthyridin-4-one-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24290Palladium ChlorideKatalysatorHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A mixture of N-isopropyl-1-(3-bromophenyl)-1,4-dihydro[1,8]naphthyridin-4-one-3-carboxamide from Step 4 of EXAMPLE 1, 2-phenyl-3-butyn-2-ol (2 eq), triethylamine (1.66 eq), bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.05 eq), and copper(I) iodide (5 mg/mmol) in DMF (20 ml/mmol) was heated at 85° C. for 18 hours. After cooling to room temperature, the resulting mixture was quenched with saturated aqueous ammonium chloride solution and partitioned between ethyl acetate and water. The crude product from the organic phase was chromatographed on silica gel eluting with 20% ether in methylene chloride. The purified product was stirred in ether at room temperature for 3 hours and filtered to afford the title compound as a white solid.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. customthe resulting mixture was quenched with saturated aqueous ammonium chloride solution
  3. custompartitioned between ethyl acetate and water
  4. customThe crude product from the organic phase was chromatographed on silica gel eluting with 20% ether in methylene chloride
  5. filtrationfiltered

Quellen und Nachweise

ORD-Eintrag
ord-dd67d90dc91049d59b4870fc9e136467
Quelldatensatz
uspto-grants-2004_06
Patentnummer
US06743802B2

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