Trifluoroacetic acid → HCID 59026713, compound

HRID 606086Notes

Reaction equation

HRID 606086 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([CH2:13][N:14]3[C:26]4[C:25]5[N:24]=[CH:23][CH:22]=[CH:21][C:20]=5[N:19]=[C:18]([NH2:27])[C:17]=4[N:16]=[CH:15]3)[O:10][N:9]=2)=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>[Pt](=O)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:12]=[C:11]([CH2:13][N:14]3[C:26]4[C:25]5[NH:24][CH2:23][CH2:22][CH2:21][C:20]=5[N:19]=[C:18]([NH2:27])[C:17]=4[N:16]=[CH:15]3)[O:10][N:9]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59026669HCID 59026669, compound

Product 1

HCID 59026713HCID 59026713, compoundYield 12.6%

Reagents, catalysts & solvents 1

HCID 345198Adams' catalystCatalyst

Procedure

1-{[3-(4-Fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine (Example 11, 0.300 g, 0.833 mmol) was combined with platinum (IV) oxide (0.03 g) and trifluoroacetic acid (5 mL), and the mixture was placed under hydrogen pressure (45 psi, 3.1×105 Pa) for 24 hours. An analysis by liquid chromatography/mass spectrometry indicated the presence of starting material. The catalyst was removed by filtration, and the trifluoroacetic acid was removed under reduced pressure. The residue was combined with trifluoroacetic acid (5 mL) and platinum (IV) oxide (0.10 g), and the reaction was again placed under hydrogen pressure (45 psi, 3.1×105 Pa) for 24 hours. The catalyst was removed by filtration, and the trifluoroacetic acid was removed under reduced pressure. The resulting oil was dissolved in 6 N hydrogen chloride in ethanol and stirred for 30 minutes. The solvent was removed under reduced pressure, and the residue was dissolved in water. The solution was adjusted to pH 14 with the addition of a few drops of 50% w/w sodium hydroxide, and the resulting mixture was stirred for 30 minutes. A precipitate was present and was isolated by filtration, purified by column chromatography on silica gel (5% to 10% CMA in chloroform), triturated with diethyl ether, filtered, and dried to provide 0.0382 g of 1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-6,7,8,9-tetrahydro-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine as a white powder, mp 227.0-228.0° C.

Workup

  1. customfor 24 hours
  2. customThe catalyst was removed by filtration
  3. customthe trifluoroacetic acid was removed under reduced pressure
  4. customfor 24 hours
  5. customThe catalyst was removed by filtration
  6. customthe trifluoroacetic acid was removed under reduced pressure
  7. dissolutionThe resulting oil was dissolved in 6 N hydrogen chloride in ethanol
  8. customThe solvent was removed under reduced pressure
  9. dissolutionthe residue was dissolved in water
  10. additionThe solution was adjusted to pH 14 with the addition of a few drops of 50% w/w sodium hydroxide
  11. stirringthe resulting mixture was stirred for 30 minutes
  12. customwas isolated by filtration
  13. custompurified by column chromatography on silica gel (5% to 10% CMA in chloroform)
  14. customtriturated with diethyl ether
  15. filtrationfiltered
  16. customdried

Sources & evidence

ORD record
ord-0eda2f45dd64497e98b96f8c4d6cff1d
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

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