Trifluoroacetic acid → HCID 57657231, compound

HRID 244876Notes

Reaction equation

HRID 244876 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:22][CH3:23])[N:14]([CH2:15][CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([CH:24]=[CH:25][C:26]#[N:27])=[CH:5][C:4]=2[N:3]=1.FC(F)(F)C(O)=O>[Pd].CO>[NH2:27][CH2:26][CH2:25][CH2:24][C:6]1[CH:7]=[CH:8][C:9]2[C:10]3[N:14]([CH2:15][CH:16]4[CH2:17][CH2:18][O:19][CH2:20][CH2:21]4)[C:13]([CH2:22][CH3:23])=[N:12][C:11]=3[C:2]([NH2:1])=[N:3][C:4]=2[CH:5]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69081100HCID 69081100, compound

Product 1

HCID 57657231HCID 57657231, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A glass Parr vessel was charged with 10% palladium on carbon (1 g), methanol (50 mL), 3-[4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]prop-2-enenitrile (4.0 g, 11.1 mmol) and trifluoroacetic acid (6.3 g, 55 mmol). The vessel was evacuated, charged with hydrogen gas (40 psi, 2.8×105 Pa) and shaken for approximately 18 hours. The mixture was filtered and concentrated under reduced pressure to a yellow oil. The oil was dissolved in 10% aqueous hydrochloric acid and stirred for 18 hours. Chloroform (100 mL) was added followed by slow addition of potassium carbonate until the pH equaled 11. The fractions were separated and the aqueous fraction was extracted with chloroform (4×50 mL). The combined organic fractions were sequentially dried (MgSO4), filtered, and concentrated under reduced pressure. Recrystallization from acetonitrile provided 3.55 g of the desired product as a white solid. A small amount of this material was further purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a CMA:chloroform gradient, 0-30% CMA over 1000 mL followed by 30% CMA over 1000 mL). A final recrystallization from acetonitrile provided 7-(3-aminopropyl)-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine as a white solid, mp 217-220° C.

Workup

  1. customThe vessel was evacuated
  2. additioncharged with hydrogen gas (40 psi, 2.8×105 Pa)
  3. filtrationThe mixture was filtered
  4. concentrationconcentrated under reduced pressure to a yellow oil
  5. dissolutionThe oil was dissolved in 10% aqueous hydrochloric acid
  6. stirringstirred for 18 hours
  7. additionChloroform (100 mL) was added
  8. additionfollowed by slow addition of potassium carbonate until the pH
  9. customThe fractions were separated
  10. extractionthe aqueous fraction was extracted with chloroform (4×50 mL)
  11. dry with materialThe combined organic fractions were sequentially dried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customRecrystallization from acetonitrile

Sources & evidence

ORD record
ord-1dc4454af762406ea1f27c222ffe3289
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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