Cesium carbonate → 2-butyl-1-methyl-8-[(5-morpholin-4-yl-5-oxopentyl)oxy]-1H-imidazo[4,5-c]quinoline

HRID 2203524Notes

Reaction equation

HRID 2203524 reaction equation
[CH2:1]([C:5]1[N:6]([CH3:19])[C:7]2[C:16]3[CH:15]=[C:14]([OH:17])[CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:18]=1)[CH2:2][CH2:3][CH3:4].C(C1N(CC(C)C)C2C3C=CC(O)=CC=3N=CC=2N=1)C.Br[CH2:41][CH2:42][CH2:43][CH2:44][C:45]([N:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1)=[O:46].BrCC(N1CCOCC1)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>C(OCC)C>[CH2:1]([C:5]1[N:6]([CH3:19])[C:7]2[C:16]3[CH:15]=[C:14]([O:17][CH2:41][CH2:42][CH2:43][CH2:44][C:45]([N:47]4[CH2:52][CH2:51][O:50][CH2:49][CH2:48]4)=[O:46])[CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:18]=1)[CH2:2][CH2:3][CH3:4]

Participants

7

Reactant 5

HCID 10796Cesium carbonateHCID 5318495-Bromopentanoic acid, morpholide2×HCID 139968762-Bromo-1-(morpholin-4-yl)ethan-1-oneHCID 670510242-butyl-1-methyl-1H-imidazo[4,5-c]quinolin-8-olHCID 1363478472-ethyl-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-ol

Product 1

HCID 689703092-butyl-1-methyl-8-[(5-morpholin-4-yl-5-oxopentyl)oxy]-1H-imidazo[4,5-c]quinolineYield 49%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

A modification of the general method described in Part D of Example 30 was followed using 2-butyl-1-methyl-1H-imidazo[4,5-c]quinolin-8-ol (1.2 g, 4.7 mmol) in lieu of 2-ethyl-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-ol and 4-(5-bromopentanoyl)morpholine (3.7 mmol) in lieu of 4-(2-bromoacetyl)morpholine. After the reaction was heated overnight, an analysis by TLC indicated the presence of starting material. Additional 4-(5-bromopentanoyl)morpholine (2.2 g) and cesium carbonate (0.5 g) were added, and the reaction was heated at 80° C. overnight. After the solution was concentrated, the residue was further dried under high vacuum overnight and then dissolved in ethyl acetate. The resulting solution was washed with water and concentrated under reduced pressure. The solid was purified by column chromatography on silica gel (eluting with 90:10 dichloromethane:methanol) to provide an oil, which was stirred with diethyl ether and allowed to stand over three days in a refrigerator. A precipitate formed, which was isolated by filtration to provide 0.770 g of 2-butyl-1-methyl-8-[(5-morpholin-4-yl-5-oxopentyl)oxy]-1H-imidazo[4,5-c]quinoline as pale yellow crystals.

Workup

  1. temperatureAfter the reaction was heated overnight
  2. concentrationAfter the solution was concentrated
  3. customthe residue was further dried under high vacuum overnight
  4. dissolutiondissolved in ethyl acetate
  5. washThe resulting solution was washed with water
  6. concentrationconcentrated under reduced pressure
  7. customThe solid was purified by column chromatography on silica gel (eluting with 90:10 dichloromethane:methanol)
  8. customto provide an oil, which
  9. customA precipitate formed
  10. customwhich was isolated by filtration

Sources & evidence

ORD record
ord-ef138c31288c49ed8773be3b9d54df95
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

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