Ethyl Acrylate → ethyl (2E)-3-[4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]prop-2-enoate

HRID 244884

Reaction equation

HRID 244884 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:15]([CH2:16][CH:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[C:14]([CH2:23][CH3:24])=[N:13][C:7]=3[C:8]([NH2:12])=[N:9][C:10]=2[CH:11]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[C:47]([O:51][CH2:52][CH3:53])(=[O:50])[CH:48]=[CH2:49]>CN(C)C=O.C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:12][C:8]1[C:7]2[N:13]=[C:14]([CH2:23][CH3:24])[N:15]([CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[C:6]=2[C:5]2[CH:4]=[CH:3][C:2](/[CH:49]=[CH:48]/[C:47]([O:51][CH2:52][CH3:53])=[O:50])=[CH:11][C:10]=2[N:9]=1

Participants

7

Reactant 3

HCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 690807877-bromo-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 57657271ethyl (2E)-3-[4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]prop-2-enoateYield 72.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent3×HCID 8471TriethylamineSolvent

Conditions

Temperature
120 °C

Procedure

A thick walled glass vessel, equipped with a stir bar, was charged with a warmed solution of 7-bromo-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine (2.5 g, 6.42 mmol) in N,N-dimethylformamide (50 mL). To the solution was added in succession, a solution of palladium acetate (144 mg, 0.642 mmol) and tri-ortho-tolylphosphine (390 mg, 1.28 mmol) in N,N-dimethylformamide (5 mL), triethylamine (2.7 mL) and a solution of ethyl acrylate (0.77 g, 7.7 mmol) in N,N-dimethylformamide (2 mL). The reaction mixture was purged with nitrogen. The vessel was sealed and heated at 120° C. for 18 hours. The reaction was cooled to ambient temperature and then concentrated to dryness under reduced pressure. The resulting solid was dissolved in dichloromethane (150 mL) and washed with saturated aqueous potassium carbonate (100 mL). The fractions were separated and the organic fraction was concentrated to dryness under reduced pressure. The resulting off-white solid was purified by chromatography using a HORIZON HPFC system (silica cartridge, 0-15% CMA/chloroform). A final recrystallization from acetonitrile provided 1.9 g of ethyl (2E)-3-[4-amino-2-ethyl-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-7-yl]prop-2-enoate as an off-white crystalline solid, mp 209-210° C.

Workup

  1. customA thick walled glass vessel, equipped with a stir bar
  2. additionTo the solution was added in succession
  3. customThe reaction mixture was purged with nitrogen
  4. customThe vessel was sealed
  5. temperatureThe reaction was cooled to ambient temperature
  6. concentrationconcentrated to dryness under reduced pressure
  7. dissolutionThe resulting solid was dissolved in dichloromethane (150 mL)
  8. washwashed with saturated aqueous potassium carbonate (100 mL)
  9. customThe fractions were separated
  10. concentrationthe organic fraction was concentrated to dryness under reduced pressure
  11. customThe resulting off-white solid was purified by chromatography
  12. customA final recrystallization from acetonitrile

Sources & evidence

ORD record
ord-c46d12fddfa547939f6da4c9638b1689
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Linked notes

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