Methanol → 1-(2-{[3-(3,4-dimethylphenyl)-2-propynyl]oxy}ethyl]-1H-imidazo[4,5-c]quinolin-4-amine

HRID 433980

Reaction equation

HRID 433980 reaction equation
[CH2:1]([O:4][CH2:5][CH2:6][N:7]1[C:19]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:12]=[C:11]([NH2:20])[C:10]=2[N:9]=[CH:8]1)[C:2]#[CH:3].I[C:22]1[CH:23]=[C:24]([CH3:29])[C:25]([CH3:28])=[CH:26][CH:27]=1.N1CCCC1.CO>C(Cl)(Cl)Cl.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:29][C:24]1[CH:23]=[C:22]([C:3]#[C:2][CH2:1][O:4][CH2:5][CH2:6][N:7]2[C:19]3[C:18]4[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=4[N:12]=[C:11]([NH2:20])[C:10]=3[N:9]=[CH:8]2)[CH:27]=[CH:26][C:25]=1[CH3:28]

Participants

8

Reactant 4

HCID 887MethanolHCID 31268PyrrolidineHCID 1416464-Iodo-1,2-dimethylbenzeneHCID 98566101-[2-(2-propynyloxy)ethyl)-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 222544631-(2-{[3-(3,4-dimethylphenyl)-2-propynyl]oxy}ethyl]-1H-imidazo[4,5-c]quinolin-4-amineYield 14.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6212ChloroformSolvent

Procedure

Under a nitrogen atmosphere, 1-[2-(2-propynyloxy)ethyl]-1H-imidazo[4,5-c]quinolin-4-amine (0.5 g, 1.9 mmol), copper (I) iodide (0.036 g, 0.2 mmol), 4-iodo-orthoxylene (0.5 g, 2.1 mmol) and pyrrolidine (10 mL) were combined and stirred at ambient temperature. Dichlorobis(triphenylphosphine)palladium(II) (0.066 g, 0.1 mmol) was added and the reaction mixture was stirred at ambient temperature for 1 hour. Analysis by TLC (30% methanol in chloroform) indicated that starting material was still present. The reaction mixture was heated at 65° C. overnight. The pyrrolidine was removed under reduced pressure. The resulting residue was triturated with dichloromethane containing methanol. The insoluble material was isolated by filtration and then recrystallized from toluene (40 mL) to provide 0.1 g of 1-(2-{[3-(3,4-dimethylphenyl)-2-propynyl]oxy}ethyl]-1H-imidazo[4,5-c]quinolin-4-amine as a solid, m.p. 214-216° C. Analysis: Calculated for C23H22N4O: %C, 74.57; %H, 5.99; %N, 15.12; Found: %C, 74.24; %H, 5.98; %N, 15.08. 1H-NMR (300 MHz; DMSO-d6) δ (ppm) 8.167(s, 1H), 8.112(d, J=7.3 Hz, 1H), 7.628(d, J=8.3 Hz, 1H), 7.44(t, J=7.3 Hz, 1H), 7.232(t, J=6.8 Hz, 1H), 7.078(d, J=7.8 Hz, 1H), 7.024(s, 1H), 6.952(d, J=7.9 Hz, 1H), 6.586(s, 2H), 4.849(t, J=5 Hz, 2H), 4.365(s, 2H), 4.015(t, J=5.6 Hz, 2H), 2.197(s, 3H), 2.159(s, 3H).

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for 1 hour
  2. temperatureThe reaction mixture was heated at 65° C. overnight
  3. customThe pyrrolidine was removed under reduced pressure
  4. customThe resulting residue was triturated with dichloromethane
  5. additioncontaining methanol
  6. customThe insoluble material was isolated by filtration
  7. customrecrystallized from toluene (40 mL)

Sources & evidence

ORD record
ord-3c8cb814284242108e2b7ba991942776
Source dataset
uspto-grants-2003_12
Patent number
US06670372B2

Linked notes

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