1,1,1-Trimethoxybutane → 7-benzyloxy-1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinoline

HRID 2203486Notes

Reaction equation

HRID 2203486 reaction equation
[C:1](OC)(OC)(OC)[CH2:2][CH2:3][CH3:4].[CH2:11]([O:18][C:19]1[CH:28]=[C:27]2[C:22]([C:23]([NH:30][CH2:31][CH:32]([CH3:34])[CH3:33])=[C:24]([NH2:29])[CH:25]=[N:26]2)=[CH:21][CH:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.Cl.N1C=CC=CC=1>C1(C)C=CC=CC=1>[CH2:11]([O:18][C:19]1[CH:20]=[CH:21][C:22]2[C:23]3[N:30]([CH2:31][CH:32]([CH3:34])[CH3:33])[C:1]([CH2:2][CH2:3][CH3:4])=[N:29][C:24]=3[CH:25]=[N:26][C:27]=2[CH:28]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 1235121,1,1-Trimethoxybutane2×HCID 10176127Pyridinium chlorideHCID 670509707-benzyloxy-N4-(2-methylpropyl)quinoline-3,4-diamine

Product 1

HCID 670509177-benzyloxy-1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinolineYield 95%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

Trimethyl orthobutyrate (29.75 mL, 0.1859 mol) was added in three portions to a solution of 7-benzyloxy-N4-(2-methylpropyl)quinoline-3,4-diamine (54.6 g, 0.170 mol) in toluene (795 mL). Pyridine hydrochloride (1.96 g) was then added, and the reaction was heated at 105° C. and stirred for four hours. Additional trimethyl orthobutyrate (7 mL, 40 mmol) was then added, and the reaction was stirred for three hours. The reaction was allowed to cool to ambient temperature, and the solvent was removed under reduced pressure. The oily residue was treated with chloroform, which was removed under reduced pressure to remove residual toluene, and then again diluted with chloroform (1.2 L). The resulting solution was washed sequentially with 5% aqueous sodium bicarbonate, water, and brine; dried over magnesium sulfate; filtered; and concentrated under reduced pressure to yield 60.3 g of 7-benzyloxy-1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c]quinoline as an oily brown solid, containing a small amount of toluene (0.93 equivalents).

Workup

  1. stirringthe reaction was stirred for three hours
  2. temperatureto cool to ambient temperature
  3. customthe solvent was removed under reduced pressure
  4. additionThe oily residue was treated with chloroform, which
  5. customwas removed under reduced pressure
  6. customto remove residual toluene
  7. additionagain diluted with chloroform (1.2 L)
  8. washThe resulting solution was washed sequentially with 5% aqueous sodium bicarbonate, water, and brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationand concentrated under reduced pressure

Sources & evidence

ORD record
ord-5bb92d7323f14b029bba1cd32ae8d564
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

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