Triphenylphosphine → 5-[4-fluoro-3-(1-methyl-1H-[1,2,3]triazol-4-ylmethoxy)phenyl]-2-trifluoromethyl[1,8]naphthyridine

HRID 1061836Notes

Reaction equation

HRID 1061836 reaction equation
[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].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[CH3:56][N:57]1[CH:61]=[C:60]([CH2:62]O)[N:59]=[N:58]1>C1COCC1>[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][CH2:62][C:60]1[N:59]=[N:58][N:57]([CH3:56])[CH:61]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 126543491-Methyl-1H-1,2,3-triazole-4-methanolHCID 222853142-Fluoro-5-(7-trifluoromethyl[1,8]naphthyridin-4-yl)phenol

Product 1

HCID 102724985-[4-fluoro-3-(1-methyl-1H-[1,2,3]triazol-4-ylmethoxy)phenyl]-2-trifluoromethyl[1,8]naphthyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-Fluoro-5-(7-trifluoromethyl[1,8]naphthyridin-4-yl)phenol (50.0 mg, 0.16 mmol), resin-bound triphenylphosphine (180 mg of 3 mmol/g resin, 5.4 mmol), diisopropylazodicarboxylate (76.8 μL, 78.8 mg, 0.40 mmol) and 1-methyl-1H-1,2,3-triazole-4-methanol (prepared as described in WO 0023449, 22.0 mg, 0.20 mmol) were stirred together in THF (3 mL) at room temperature overnight. The mixture was filtered, and the filtrate was diluted with dichloromethane (15 mL), was washed with 1 N sodium hydroxide (2×10 mL), was dried over magnesium sulfate and was concentrated in vacuo. The residue was purified by flash chromatography on silica gel, eluting with 2.5% methanol in dichloromethane, affording 5-[4-fluoro-3-(1-methyl-1H-[1,2,3]triazol-4-ylmethoxy)phenyl]-2-trifluoromethyl[1,8]naphthyridine as a colourless solid, which was recrystallised from ethyl acetate/isohexane (26.7 mg, 41%). δH (360 MHz, CDCl3) 4.13 (3H, s), 5.35 (2H, s), 7.03-7.07 (1H, m), 7.25-7.31 (1H, m), 7.38 (1H, dd, J 2.1 and 7.7), 7.54 (1H, d, J 4.6), 7.70 (1H, s), 7.86 (1H, d, J 8.8), 8.53 (1H, d, J 8.8), 9.26 (1H, d, J 4.2). m/z (ES+) 404 [MH]+.

Workup

  1. filtrationThe mixture was filtered
  2. additionthe filtrate was diluted with dichloromethane (15 mL)
  3. washwas washed with 1 N sodium hydroxide (2×10 mL)
  4. dry with materialwas dried over magnesium sulfate
  5. concentrationwas concentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel
  7. washeluting with 2.5% methanol in dichloromethane

Sources & evidence

ORD record
ord-94d9752d35dc4c6b8d87f44f70dbb08f
Source dataset
uspto-grants-2005_11
Patent number
US06960598B2

Reaction notes

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