Potassium Carbonate → 2-(Tetrahydro-2H-pyran-2-yl)-5-((6-(trifluoromethyl)pyridin-3-yl)methoxy)pyridazin-3(2H)-one

HRID 474934

Reaktionsgleichung

Reaktionsgleichung von HRID 474934
[OH:1][C:2]1[CH:7]=[N:6][N:5]([CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][O:9]2)[C:4](=[O:14])[CH:3]=1.Br[CH2:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]([F:26])([F:25])[F:24])=[N:21][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(Cl)Cl>[O:9]1[CH2:10][CH2:11][CH2:12][CH2:13][CH:8]1[N:5]1[C:4](=[O:14])[CH:3]=[C:2]([O:1][CH2:16][C:17]2[CH:22]=[N:21][C:20]([C:23]([F:26])([F:24])[F:25])=[CH:19][CH:18]=2)[CH:7]=[N:6]1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 144051255-(Bromomethyl)-2-(trifluoromethyl)pyridineHCID 579503555-Hydroxy-2-(2-tetrahydropyranyl)pyridazin-3(2H)-one

Produkt 1

HCID 668688942-(Tetrahydro-2H-pyran-2-yl)-5-((6-(trifluoromethyl)pyridin-3-yl)methoxy)pyridazin-3(2H)-oneAusbeute 123,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

5-Hydroxy-2-(tetrahydro-2H-pyran-2-yl)pyridazin-3(2H)-one (2.3 g, 12 mmol), 5-(bromomethyl)-2-(trifluoromethyl)pyridine (7.2 g, 30 mmol) and K2CO3 (8.4 g, 60 mmol) were stirred in DMF (40 ml) and CH2Cl2 (40 ml) for 48 h. The mixture was diluted with CH2Cl2, washed with 5% LiCl solution (4×) and concentrated. The residue was purified by column chromatography (40 g ISCO column column eluting with methylene chloride and a 10:1 methanol/ammonium hydroxide mixture; gradient 100% methylene chloride to 95% methylene chloride) to yield the title compound (5.25 g, >100%) as a waxy white solid containing some DMF: 1H NMR (300 MHz, CDCl3) δ 8.78 (d, J=1.8 Hz, 1H), 7.97-7.88 (m, 1H), 7.76 (d, J=7.9 Hz, 1H), 7.72 (m, 1H), 6.20 (d, J=2.9 Hz, 1H), 6.03-5.98 (d, J=10.9, 2.0 Hz, 1H), 5.11 (s, 2H), 4.16-4.08 (m, 1H), 3.79-3.69 (m, 1H), 2.24-1.96 (m, 2H), 1.83-1.48 (m, 4H).

Aufarbeitung

  1. washwashed with 5% LiCl solution (4×)
  2. concentrationconcentrated
  3. customThe residue was purified by column chromatography (40 g ISCO column column
  4. washeluting with methylene chloride

Quellen und Nachweise

ORD-Eintrag
ord-04101919e5954239b255875565c24114
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08637501B2

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