Trifluoroacetic acid → HCID 57447060, compound

HRID 2366669Notes

Reaction equation

HRID 2366669 reaction equation
[N:1]1([C:7](=[O:28])[CH2:8][CH2:9][CH2:10][N:11]2[C:23]3[C:22]4[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=4[N:16]=[C:15]([NH2:24])[C:14]=3[N:13]=[C:12]2[CH2:25][CH2:26][CH3:27])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.FC(F)(F)C(O)=O>[Pt](=O)=O>[N:1]1([C:7](=[O:28])[CH2:8][CH2:9][CH2:10][N:11]2[C:23]3[C:22]4[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=4[N:16]=[C:15]([NH2:24])[C:14]=3[N:13]=[C:12]2[CH2:25][CH2:26][CH3:27])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 11474498HCID 11474498, compound

Product 1

HCID 57447060HCID 57447060, compoundYield 92.5%

Reagents, catalysts & solvents 1

HCID 345198Adams' catalystCatalyst2×

Procedure

A mixture of 1-(4-morpholin-4-yl-4-oxobutyl)-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine (0.62 g, 1.6 mmol, prepared as described in Example 1), platinum (IV) oxide (0.25 g, 1.1 mmol), and trifluoroacetic acid (25 mL) was placed in a Parr vessel and shaken under hydrogen pressure (50 psi, 3.5×105 Pa) for two hours. An analysis by LC/MS indicated the reaction was incomplete. Additional platinum (IV) oxide (0.5 g) was added, and the reaction was continued overnight. The trifluoroacetic acid was removed under reduced pressure, and the residue was dissolved in methanol (35 mL). Aqueous sodium hydroxide (10 mL of 25%) was added to the solution, and the mixture was stirred for 15 minutes and then diluted with dichloromethane (100 mL). The mixture was filtered through a layer of CELITE filter aid, and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane, washed with 5% aqueous sodium hydroxide (2×25 mL), dried over potassium carbonate, filtered, and concentrated under reduced pressure. The resulting solid was recrystallized from water:acetonitrile; the crystals were triturated with 25% aqueous sodium hydroxide for one hour, diluted with water, isolated by filtration, and recrystallized from water:ethanol. The resulting crystals were dried overnight in a vacuum oven at 70° C. to provide 0.5706 g of l-(4-morpholin-4-yl-4-oxobutyl)-2-propyl-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-4-amine as white crystals, mp 181-183° C.

Workup

  1. waitthe reaction was continued overnight
  2. customThe trifluoroacetic acid was removed under reduced pressure
  3. dissolutionthe residue was dissolved in methanol (35 mL)
  4. additionAqueous sodium hydroxide (10 mL of 25%) was added to the solution
  5. stirringthe mixture was stirred for 15 minutes
  6. additiondiluted with dichloromethane (100 mL)
  7. filtrationThe mixture was filtered through a layer of CELITE
  8. filtrationfilter aid
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. dissolutionThe residue was dissolved in dichloromethane
  11. washwashed with 5% aqueous sodium hydroxide (2×25 mL)
  12. dry with materialdried over potassium carbonate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe resulting solid was recrystallized from water
  16. customthe crystals were triturated with 25% aqueous sodium hydroxide for one hour
  17. additiondiluted with water
  18. customisolated by filtration
  19. customrecrystallized from water
  20. customThe resulting crystals were dried overnight in a vacuum oven at 70° C.

Sources & evidence

ORD record
ord-5e3c2ee55c384f3eba7e62716878718a
Source dataset
uspto-grants-2014_04
Patent number
US08697873B2

Reaction notes

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