Hydrochloric Acid → HCID 57515416, compound

HRID 44733Notes

Reaction equation

HRID 44733 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:22][O:23][CH2:24][CH3:25])[N:14]([CH2:15][C:16]3([OH:21])[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.Cl>FC(F)(F)C(O)=O.C(O)C.[Pt](=O)=O>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:22][O:23][CH2:24][CH3:25])[N:14]([CH2:15][C:16]3([OH:21])[CH2:17][CH2:18][CH2:19][CH2:20]3)[C:10]=2[C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[N:3]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 57515381HCID 57515381, compound

Product 1

HCID 57515416HCID 57515416, compound

Reagents, catalysts & solvents 3

HCID 345198Adams' catalystCatalystHCID 702EthanolSolvent2×HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 1-{[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclopentanol (prepared as described in Example 3, 0.50 g, 1.47 mmol) and platinum (IV) oxide (0.25 g) in trifluoroacetic acid (20 mL) was hydrogenated at 50 psi (3.5×105 Pa) for 5 d on a Parr apparatus. The reaction mixture was filtered through CELITE filter agent and the filtrate was treated with saturated aqueous NaOH until the pH=14, then was extracted with dichloromethane (3×100 mL). The organic layers were combined, dried over MgSO4, filtered, and concentrated to an oil that was purified by flash chromatography (silica gel, 10% methanol in dichloromethane). The appropriate fractions were combined and concentrated to yield a colorless oil. The oil was dissolved in ethanol and 2.7 M HCl in ethanol (1 mL) was added and the mixture was concentrated under reduced pressure. The resulting oil was dissolved in water and Na2CO3 was added until the pH=12. A gummy white solid formed and the mixture was heated at 60° C. for 20 min until a free flowing precipitate formed. The mixture was allowed to cool to rt and the precipitate was isolated by filtration and dried in a vacuum oven at 80° C. to provide 1-{[4-amino-2-(ethoxymethyl)-6,7,8,9-tetrahydro-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclopentanol as a white solid, mp 171-173° C. 1H NMR (300 MHz, DMSO-d6) δ 5.78 (br s, 2H), 4.77 (br s, 2H), 4.66 (s, 1H), 4.45 (br s, 2H), 3.46 (q, J=7.0 Hz, 2H), 2.95 (m, 2H), 2.66 (m, 2H), 1.82-1.36 (m, 12H), 1.11 (t, J=7.0 Hz, 3H); MS (ESI) m/z 345 (M+H)+; Anal. Calcd for C19H28N4O20.2 H2O: C, 65.57; H, 8.22; N, 16.10. Found: C, 65.78; H, 8.27; N, 15.70.

Workup

  1. filtrationThe reaction mixture was filtered through CELITE
  2. filtrationfilter agent
  3. additionthe filtrate was treated with saturated aqueous NaOH until the pH=14
  4. extractionwas extracted with dichloromethane (3×100 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to an oil that
  8. customwas purified by flash chromatography (silica gel, 10% methanol in dichloromethane)
  9. concentrationconcentrated
  10. customto yield a colorless oil
  11. concentrationthe mixture was concentrated under reduced pressure
  12. dissolutionThe resulting oil was dissolved in water
  13. additionNa2CO3 was added until the pH=12
  14. customA gummy white solid formed
  15. customformed
  16. temperatureto cool to rt
  17. customthe precipitate was isolated by filtration
  18. customdried in a vacuum oven at 80° C.

Sources & evidence

ORD record
ord-2054fe514ba34afb90e2f5e1fda6b566
Source dataset
uspto-grants-2013_09
Patent number
US08541438B2

Reaction notes

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