Hydrochloric Acid → 4-Amino-1-isobutyl-7-methoxycarbonyl-1H-imidazo[4,5-c]-quinoline

HRID 574011Notes

Reaction equation

HRID 574011 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=1[C:12]1[N:16]([CH2:17][CH:18]([CH3:20])[CH3:19])[CH:15]=[N:14][C:13]=1[C:21]#[N:22].Cl.O1CCOCC1>>[NH2:22][C:21]1[C:13]2[N:14]=[CH:15][N:16]([CH2:17][CH:18]([CH3:19])[CH3:20])[C:12]=2[C:3]2[CH:4]=[CH:5][C:6]([C:8]([O:10][CH3:11])=[O:9])=[CH:7][C:2]=2[N:1]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 867279625-(2-amino-4-methoxycarbonylphenyl)-1-isobutyl-1H-imidazole-4-carbonitrile

Product 1

HCID 712840534-Amino-1-isobutyl-7-methoxycarbonyl-1H-imidazo[4,5-c]-quinolineYield 88%

Conditions

Temperature
25 °C

Procedure

To 5-(2-amino-4-methoxycarbonylphenyl)-1-isobutyl-1H-imidazole-4-carbonitrile S12 (150 mg, 0.50 mmol, 1.0 equiv) was added 4 N HCl in dioxane (2.0 mL, 8.0 mmol, 16 equiv). The reaction was heated at reflux condition for 15 h then cooled to 25° C. The reaction was concentrated in vacuo and partitioned between 1:9 MeOH/EtOAc (50 mL) and saturated aqueous NaHCO3 solution (10 mL). The aqueous layer was extracted with 1:9 MeOH/EtOAc (3×10 mL). The combined organic layers were washed with saturated aqueous NaCl, dried (MgSO4), and concentrated in vacuo. Purification by flash column chromatography on silica gel (CH2Cl2-1/9 MeOH/CH2Cl2, gradient) afforded the title compound 412 (132 mg, 88%) as an off white solid: 1H NMR (CD3OD, 600 Hz) δ 1.01 (d, J=6.6 Hz, 6H), 2.26 (non, J=7.2 Hz, 1H), 3.96 (s, 3H), 4.43 (d, J=7.8 Hz, 2H), 7.89 (dd, J=7.8, 1.8 Hz, 1H), 8.05 (d, J=7.8 Hz, 1H), 8.19 (s, 1H), 8.32 (d, J=1.8 Hz, 1H); 13C NMR (CD3OD, 150 Hz) δ 18.4, 28.7, 51.4, 54.2, 117.9, 120.5, 121.8, 127.1, 128.6, 128.8, 132.1, 143.6, 144.3, 152.5, 167.0; MS (APCI+): calcd C16H19N4O2 [M+H]+ 299.2. found 299.2.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux condition for 15 h
  3. concentrationThe reaction was concentrated in vacuo
  4. custompartitioned between 1:9 MeOH/EtOAc (50 mL) and saturated aqueous NaHCO3 solution (10 mL)
  5. extractionThe aqueous layer was extracted with 1:9 MeOH/EtOAc (3×10 mL)
  6. washThe combined organic layers were washed with saturated aqueous NaCl
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customPurification by flash column chromatography on silica gel (CH2Cl2-1/9 MeOH/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-17b7317259944edca5e64fd69d3a4d76
Source dataset
uspto-grants-2015_05
Patent number
US09034336B2

Reaction notes

Loading…