Hydrochloric Acid → HCID 69506715, compound

HRID 2366666Notes

Reaction equation

HRID 2366666 reaction equation
[CH3:1][C:2]([CH3:25])([CH2:8][N:9]1[C:21]2[C:20]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[N:14]=[CH:13][C:12]=2[N:11]=[C:10]1[CH2:22][CH2:23][CH3:24])[C:3](OCC)=[O:4].[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.[OH-].[Na+].Cl.C(Cl)(=O)C(Cl)=O>ClCCl>[CH3:25][C:2]([CH3:1])([C:3]([N:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)=[O:4])[CH2:8][N:9]1[C:21]2[C:20]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[N:14]=[CH:13][C:12]=2[N:11]=[C:10]1[CH2:22][CH2:23][CH3:24]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8083Morpholine2×HCID 14798Sodium HydroxideHCID 65578Oxalyl chloride2×HCID 57447057HCID 57447057, compound

Product 1

HCID 69506715HCID 69506715, compoundYield 101.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Conditions

Temperature
165 °C

Procedure

A solution of ethyl 2,2-dimethyl-3-(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propanoate (5.1 g, 15 mmol) and morpholine (5 mL, 60 mmol) was heated at reflux overnight. An analysis by LC/MS indicated the reaction was incomplete. The solution was then heated overnight in a high-pressure vessel at 165° C. Again, an analysis by LC/MS indicated the reaction was incomplete. The volatiles were removed under reduced pressure, and the residue was dissolved in ethanol (30 mL). Aqueous sodium hydroxide (1.35 mL of 50%, 20.0 mmol) was added, and the reaction was stirred for 1.5 hours. The solution was adjusted to pH 7 with the addition of concentrated hydrochloric acid (˜1 mL) and then concentrated under reduced pressure. The residue was dissolved in dichloromethane (75 mL); a solution of oxalyl chloride (2.5 mL, 28 mmol) in dichloromethane (5 mL) was added dropwise over a period of two minutes. The reaction was stirred for 30 minutes, and additional oxalyl chloride (0.5 mL, 6 mmol) was added. The reaction was stirred for 30 minutes and diluted with dichloromethane (75 mL). A solution of morpholine (4.0 mL, 41 mmol) in dichloromethane (10 mL) was then added dropwise, and the reaction was stirred for two hours. The reaction was diluted with dichloromethane (45 mL), washed with saturated aqueous sodium bicarbonate (3×50 mL), dried over potassium carbonate, filtered, and concentrated under reduced pressure. The resulting dark oil was purified by column chromatography on silica gel (eluting with 93:7 dichloromethane:methanol) to provide 5.8 g of 1-(2,2-dimethyl-3-morpholin-4-yl-3-oxopropyl)-2-propyl-1H-imidazo[4,5-c]quinoline as a semi-solid.

Workup

  1. temperatureat reflux overnight
  2. customThe volatiles were removed under reduced pressure
  3. dissolutionthe residue was dissolved in ethanol (30 mL)
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in dichloromethane (75 mL)
  6. stirringThe reaction was stirred for 30 minutes
  7. stirringThe reaction was stirred for 30 minutes
  8. stirringthe reaction was stirred for two hours
  9. washwashed with saturated aqueous sodium bicarbonate (3×50 mL)
  10. dry with materialdried over potassium carbonate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe resulting dark oil was purified by column chromatography on silica gel (eluting with 93:7 dichloromethane:methanol)

Sources & evidence

ORD record
ord-800c7923e58c4611a0ba1598898ddc32
Source dataset
uspto-grants-2014_04
Patent number
US08697873B2

Reaction notes

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