Dimethylformamide → 2-methoxymethyl-8-(3-morpholin-4-ylpropoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

HRID 540935Notes

Reaction equation

HRID 540935 reaction equation
C(=O)([O-])[O-].[K+].[K+].[NH:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.Cl[CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:27]=[CH:26][C:25]2[N:24]=[C:23]([NH2:28])[C:22]3[N:29]=[C:30]([CH2:35][O:36][CH3:37])[N:31]([CH2:32][CH2:33][CH3:34])[C:21]=3[C:20]=2[CH:19]=1.CN(C=O)C>O>[CH3:37][O:36][CH2:35][C:30]1[N:31]([CH2:32][CH2:33][CH3:34])[C:21]2[C:20]3[CH:19]=[C:18]([O:17][CH2:16][CH2:15][CH2:14][N:7]4[CH2:12][CH2:11][O:10][CH2:9][CH2:8]4)[CH:27]=[CH:26][C:25]=3[N:24]=[C:23]([NH2:28])[C:22]=2[N:29]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8083MorpholineHCID 11430Potassium CarbonateHCID 689690038-(3-chloropropoxy)-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 588336222-methoxymethyl-8-(3-morpholin-4-ylpropoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amineYield 9.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

Potassium carbonate (530 mg, 3.84 mmol), morpholine (92 mg, 1.06 mmol), and 8-(3-chloropropoxy)-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine (350 mg, 0.96 mmol) were added to 15 mL of DMF and heated to 50° C. for 18 hours. Analysis by LC/MS indicated the presence of two peaks and the reaction mixture was cooled and poured into 500 mL of deionized water. After three hours, no precipitation was observed. Sodium chloride (250 g) was added to the mixture and the mixture was stirred vigorously overnight. The precipitate was collected by filtration, dissolved in dichloromethane, and purified by chromatography on a HORIZON HPFC system (eluting with a gradient of methanol/dichloromethane (20:80) in dichloromethane from 0:100 to 40:60). The resulting material was concentrated under reduced pressure, crystallized from acetonitrile, and dried under high vacuum to yield 36 mg of 2-methoxymethyl-8-(3-morpholin-4-ylpropoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine as tan crystals, mp 193-196° C.

Workup

  1. temperaturethe reaction mixture was cooled
  2. customno precipitation
  3. additionSodium chloride (250 g) was added to the mixture
  4. filtrationThe precipitate was collected by filtration
  5. dissolutiondissolved in dichloromethane
  6. custompurified by chromatography on a HORIZON HPFC system (
  7. washeluting with a gradient of methanol/dichloromethane (20:80) in dichloromethane from 0:100 to 40:60)
  8. concentrationThe resulting material was concentrated under reduced pressure
  9. customcrystallized from acetonitrile
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-38c36e8db8f04f9197e0dd65724c31b1
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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