4-Vinylpyridine → 1-(2-methylpropyl)-8-(2-pyridin-4-ylvinyl)-1H-imidazo[4,5-c]-quinolin-4-amine

HRID 9449

Reaction equation

HRID 9449 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[C:7]([NH2:12])[C:6]3[N:13]=[CH:14][N:15]([CH2:16][CH:17]([CH3:19])[CH3:18])[C:5]=3[C:4]=2[CH:3]=1.[CH:20]([C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1)=[CH2:21].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:18][CH:17]([CH3:19])[CH2:16][N:15]1[C:5]2[C:4]3[CH:3]=[C:2]([CH:21]=[CH:20][C:22]4[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=4)[CH:11]=[CH:10][C:9]=3[N:8]=[C:7]([NH2:12])[C:6]=2[N:13]=[CH:14]1

Participants

7

Reactant 4

HCID 75024-VinylpyridineHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 111745978-bromo-1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 688187741-(2-methylpropyl)-8-(2-pyridin-4-ylvinyl)-1H-imidazo[4,5-c]-quinolin-4-amineYield 65.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

Nitrogen was bubbled through a solution of 8-bromo-1-(2-methylpropyl)-1H-imidazo[4,5-c]-quinolin-4-amine (3.0 g, 9.4 mmol), 4-vinylpyridine (2.0 mL, 19 mmol), triphenylphosphine (246 mg, 0.94 mmol), and triethylamine (2.7 mL, 19 mmol) in acetonitrile (50 mL) for 15 minutes. Palladium (II) acetate (105 mg, 0.47 mmol) was added, and the reaction was heated at 100° C. for three days. The solvent was removed under reduced pressure, and the residue was adjusted to pH 2 with the addition of concentrated hydrochloric acid. Water was added, and the mixture was filtered through a layer of CELITE filter aid. Aqueous sodium carbonate (2 N) was added to the filtrate to adjust the solution to pH 10. The solution was then extracted with dichloromethane, and the combined extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel (eluting with chloroform:CMA in a gradient from 95:5 to 80:20) to provide 2.1 g of 1-(2-methylpropyl)-8-(2-pyridin-4-ylvinyl)-1H-imidazo[4,5-c]-quinolin-4-amine as a yellow solid.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe residue was adjusted to pH 2 with the addition of concentrated hydrochloric acid
  3. additionWater was added
  4. filtrationthe mixture was filtered through a layer of CELITE
  5. filtrationfilter aid
  6. additionAqueous sodium carbonate (2 N) was added to the filtrate
  7. extractionThe solution was then extracted with dichloromethane
  8. dry with materialthe combined extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified by flash column chromatography on silica gel (
  12. washeluting with chloroform

Sources & evidence

ORD record
ord-06dcb0dc9288479ba77db93b0ebf51a7
Source dataset
uspto-grants-2006_08
Patent number
US07091214B2

Linked notes

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