Sodium Chloride → 2-(ethoxymethyl)-1-propyl-8-(tetrahydrofuran-2-ylmethoxy)-1H-imidazo[4,5-c]quinolin-4-amine

HRID 540950Notes

Reaction equation

HRID 540950 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:7](Br)[CH:8]1[O:12][CH2:11][CH2:10][CH2:9]1.[NH2:14][C:15]1[C:24]2[N:25]=[C:26]([CH2:31][O:32][CH2:33][CH3:34])[N:27]([CH2:28][CH2:29][CH3:30])[C:23]=2[C:22]2[CH:21]=[C:20]([OH:35])[CH:19]=[CH:18][C:17]=2[N:16]=1.[Cl-].[Na+]>CN(C=O)C.O>[CH2:33]([O:32][CH2:31][C:26]1[N:27]([CH2:28][CH2:29][CH3:30])[C:23]2[C:22]3[CH:21]=[C:20]([O:35][CH2:7][CH:8]4[CH2:9][CH2:10][CH2:11][O:12]4)[CH:19]=[CH:18][C:17]=3[N:16]=[C:15]([NH2:14])[C:24]=2[N:25]=1)[CH3:34]

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 10796Cesium carbonateHCID 14501Furan, 2-(bromomethyl)tetrahydro-HCID 689719384-amino-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol

Product 1

HCID 588337242-(ethoxymethyl)-1-propyl-8-(tetrahydrofuran-2-ylmethoxy)-1H-imidazo[4,5-c]quinolin-4-amineYield 67.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

Cesium carbonate (1.62 g, 5.00 mmol) was added to a solution of tetrahydrofurfuryl bromide (330 mg, 1.99 mmol) and 4-amino-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol (500 mg, 1.66 mmol, prepared in Parts A and B of Example 566) in anhydrous DMF (20 mL). The reaction mixture was heated at 75° C. overnight, allowed to cool, and poured into deionized water (300 mL). After 30 minutes of stirring, a brown precipitate formed. Sodium chloride (100 g) was added, and the resulting mixture was stirred for three hours and then filtered. The isolated precipitate was purified by chromatography on a HORIZON HPFC system (silica cartridge, eluting with a gradient of 0-35% methanol/dichloromethane (10:90) in dichloromethane). The resulting solid was recrystallized from acetonitrile and dried under high vacuum to yield 429 mg of 2-(ethoxymethyl)-1-propyl-8-(tetrahydrofuran-2-ylmethoxy)-1H-imidazo[4,5-c]quinolin-4-amine as a fluffy, white solid, mp 178-179° C. Anal. calcd for C21H28N4O3.0.25H2O: C, 64.84; H, 7.39; N, 14.40. Found: C, 65.03; H, 7.75; N, 14.48.

Workup

  1. temperatureto cool
  2. customa brown precipitate formed
  3. stirringthe resulting mixture was stirred for three hours
  4. filtrationfiltered
  5. customThe isolated precipitate was purified by chromatography on a HORIZON HPFC system (silica cartridge
  6. washeluting with a gradient of 0-35% methanol/dichloromethane (10:90) in dichloromethane)
  7. customThe resulting solid was recrystallized from acetonitrile
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-f1557cbb27b54c818cb353031f8b3962
Source dataset
uspto-grants-2014_10
Patent number
US08871782B2

Reaction notes

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