Triethylamine → 2-ethoxymethyl-7-(pyridin-3-yl)-1-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]methyl}-1H-imidazo[4,5-c]quinolin-4-amine

HRID 1818144Notes

Reaction equation

HRID 1818144 reaction equation
Cl.Cl.Cl.[CH2:4]([O:6][CH2:7][C:8]1[N:9]([CH2:28][CH:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[C:10]2[C:19]3[CH:18]=[CH:17][C:16]([C:20]4[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=4)=[CH:15][C:14]=3[N:13]=[C:12]([NH2:26])[C:11]=2[N:27]=1)[CH3:5].C(N(CC)CC)C.[O:42]1[CH2:46][CH2:45][CH2:44][CH:43]1[C:47](O)=[O:48].Cl.CON(OC)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>C(Cl)(Cl)Cl>[CH2:4]([O:6][CH2:7][C:8]1[N:9]([CH2:28][CH:29]2[CH2:30][CH2:31][N:32]([C:47]([CH:43]3[CH2:44][CH2:45][CH2:46][O:42]3)=[O:48])[CH2:33][CH2:34]2)[C:10]2[C:19]3[CH:18]=[CH:17][C:16]([C:20]4[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=4)=[CH:15][C:14]=3[N:13]=[C:12]([NH2:26])[C:11]=2[N:27]=1)[CH3:5]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 86079(+-)-Tetrahydro-2-furoic acidHCID 219842792-ethoxymethyl-1-(piperidin-4-ylmethyl)-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-4-amine trihydrochlorideHCID 219844591-(3-Dimethoxyaminopropyl)-3-ethylcarbodiimide hydrochloride

Product 1

HCID 219841412-ethoxymethyl-7-(pyridin-3-yl)-1-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]methyl}-1H-imidazo[4,5-c]quinolin-4-amineYield 69.5%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Conditions

Temperature
4 °C

Procedure

A solution of 2-ethoxymethyl-1-(piperidin-4-ylmethyl)-7-(pyridin-3-yl)-1H-imidazo[4,5-c]quinolin-4-amine trihydrochloride (1.0 g, 1.90 mmol) and triethylamine (1.35 mL, 9.50 mmol) in chloroform (80 mL) was cooled to 4° C. 2-Tetrahydrofuroic acid (0.243 g, 2.09 mmol) and 1-(3-dimethoxyaminopropyl)-3-ethylcarbodiimide hydrochloride (0.401 g, 2.09 mmol) were sequentially added, and the reaction was stirred for two hours. The reaction was incomplete as determined by thin layer chromatography (TLC) analysis. The reaction was cooled to 4° C., and 1-hydroxybenzotriazole (0.283 g, 2.09 mmol) was added. The reaction was allowed to warm to ambient temperature, stirred for 16 hours, and then diluted with chloroform (100 mL). The resulting solution was washed sequentially with water (100 mL), 4% aqueous sodium carbonate (2×100 mL), water (200 mL), and brine (150 mL); dried over sodium sulfate; filtered; and concentrated under reduced pressure. The residue was purified by HPFC followed by recrystallization from ethyl acetate to provide 0.68 g of 2-ethoxymethyl-7-(pyridin-3-yl)-1-{[1-(tetrahydrofuran-2-ylcarbonyl)piperidin-4-yl]methyl}-1H-imidazo[4,5-c]quinolin-4-amine as a white, crystalline solid, mp 191-192° C.

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for 16 hours
  3. washThe resulting solution was washed sequentially with water (100 mL), 4% aqueous sodium carbonate (2×100 mL), water (200 mL), and brine (150 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationand concentrated under reduced pressure
  7. customThe residue was purified by HPFC
  8. customfollowed by recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-9f958a534e8e452ab563a85eeeea3238
Source dataset
uspto-grants-2009_10
Patent number
US07598382B2

Reaction notes

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