Cesium carbonate → 5-[4-Fluoro-3-(pyridin-3-ylmethoxy)phenyl]-2-trifluoromethyl[1,8]naphthyridine

HRID 1061831Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1061831
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[N:13][C:14]([C:18]([F:21])([F:20])[F:19])=[CH:15][CH:16]=3)[N:11]=[CH:10][CH:9]=2)=[CH:4][C:3]=1[OH:22].C(=O)([O-])[O-].[Cs+].[Cs+].Cl.Cl[CH2:31][C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][N:11]=[C:12]3[C:17]=2[CH:16]=[CH:15][C:14]([C:18]([F:19])([F:20])[F:21])=[N:13]3)=[CH:4][C:3]=1[O:22][CH2:31][C:32]1[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=1

Komponenten

5

Edukt 3

HCID 10796Cesium carbonateHCID 233943-(Chloromethyl)pyridine hydrochlorideHCID 222853142-Fluoro-5-(7-trifluoromethyl[1,8]naphthyridin-4-yl)phenol

Produkt 1

HCID 102225505-[4-Fluoro-3-(pyridin-3-ylmethoxy)phenyl]-2-trifluoromethyl[1,8]naphthyridine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

2-Fluoro-5-(7-trifluoromethyl[1,8]naphthyridin-4-yl)phenol (prepared as described in Example 35 part a), 50.0 mg, 0.16 mmol), caesium carbonate (159 mg, 0.49 mmol) and 3-(chloromethyl)pyridine hydrochloride (31.9 mg, 0.20 mmol) were stirred together in DMF (3 mL) at room temperature under nitrogen overnight. The mixture was partitioned between dichloromethane (3 mL) and water (3 mL), then was filtered through a PTFE cartridge. The separated organic phase was concentrated in vacuo, and residue was purified by flash chromatography on silica gel, eluting with 1:1 dichloromethane:ethyl acetate, then with ethyl acetate, affording 5-[4-fluoro-3-(pyridin-3-ylmethoxy)phenyl]-2-trifluoromethyl[1,8]naphthyridine as a colourless oil, which solidified upon trituration with isohexane (45.1 mg, 70%). δH (400 MHz, CDCl3) 5.22 (2H, s), 7.06-7.12 (2H, m), 7.30-7.38 (2H, m), 7.52 (1H, d, J 4.3), 7.79 (1H, d, J 8.6), 7.81-7.83 (1H, m), 8.39 (1H, d, J 8.6), 8.64 (1H, dd, J 1.6 and 4.7), 8.69 (1H, d, J 2.0), 9.26 (1H, d, J 4.3). m/z (ES+) 400 [MH]+.

Aufarbeitung

  1. customThe mixture was partitioned between dichloromethane (3 mL) and water (3 mL)
  2. filtrationwas filtered through a PTFE cartridge
  3. concentrationThe separated organic phase was concentrated in vacuo, and residue
  4. customwas purified by flash chromatography on silica gel
  5. washeluting with 1:1 dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-ee37af84f32c4a8ebbcbf10fe8e4609b
Quelldatensatz
uspto-grants-2005_11
Patentnummer
US06960598B2

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