Trifluoroacetic acid → HCID 69082296, compound

HRID 244852Notes

Reaction equation

HRID 244852 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]1[C:18]2[N:19]=[C:20]([CH2:27][O:28][CH3:29])[N:21]([CH2:22][C:23]([OH:26])([CH3:25])[CH3:24])[C:17]=2[C:16]2[CH:15]=[CH:14][C:13]([CH:30]=[CH:31][C:32]#[N:33])=[CH:12][C:11]=2[N:10]=1>[Pd].CO>[NH2:8][C:9]1[C:18]2[N:19]=[C:20]([CH2:27][O:28][CH3:29])[N:21]([CH2:22][C:23]([CH3:24])([OH:26])[CH3:25])[C:17]=2[C:16]2[CH:15]=[CH:14][C:13]([CH2:30][CH2:31][CH2:32][NH2:33])=[CH:12][C:11]=2[N:10]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69082194HCID 69082194, compound

Product 1

HCID 69082296HCID 69082296, compoundYield 90.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A glass Parr vessel was charged with 10% palladium on carbon (1.0 g), methanol (200 mL), trifluoroacetic acid (5.4 mL, 72.5 mmol) and 3-[4-amino-1-(2-hydroxy-2-methylpropyl)-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-7-yl]prop-2-enenitrile (5.1 g, 14.5 mmol). The vessel was evacuated and charged with hydrogen gas (40 psi, 2.8×105 Pa). The mixture was shaken for approximately 18 hours and then filtered through a 0.2 micron PTFE membrane filter and concentrated under reduced pressure. The resulting yellow oil was dissolved in 10% aqueous hydrochloric acid (100 mL) and stirred for 30 minutes. The solution was made basic (pH 10) by the slow addition of potassium carbonate. Potassium hydroxide was added until pH equaled 13. The solution was then concentrated under reduced pressure. The resulting off-white solid was slurried in hot methanol (300 mL) and filtered. The hot methanol slurry procedure was repeated. The combined filtrates were concentrated and purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a CMA:chloroform gradient; 0-30% CMA) to provide 4.7 g of 1-[4-amino-7-(3-aminopropyl)-2-(methoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]-2-methylpropan-2-ol as an off-white foam. MS (APCI) m/z 358 (M+H)+.

Workup

  1. customThe vessel was evacuated
  2. additioncharged with hydrogen gas (40 psi, 2.8×105 Pa)
  3. filtrationfiltered through a 0.2 micron PTFE membrane
  4. filtrationfilter
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe resulting yellow oil was dissolved in 10% aqueous hydrochloric acid (100 mL)
  7. stirringstirred for 30 minutes
  8. additionby the slow addition of potassium carbonate
  9. additionPotassium hydroxide was added until pH equaled 13
  10. concentrationThe solution was then concentrated under reduced pressure
  11. filtrationfiltered
  12. concentrationThe combined filtrates were concentrated
  13. custompurified by chromatography
  14. washeluting with a CMA

Sources & evidence

ORD record
ord-053de0cbbbd141f8b1208213b9315799
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

Loading…