Sodium Chloride → 1-(4-amino-2-ethoxymethyl-7-[2-(1H-indol-3-yl)ethoxy]-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol

HRID 2383185Notes

Reaction equation

HRID 2383185 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([OH:24])=[CH:5][C:4]=2[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:32][CH2:33][C:34]1[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[NH:36][CH:35]=1.[Cl-].[Na+]>O.CN(C=O)C>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([CH3:18])([OH:19])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([O:24][CH2:32][CH2:33][C:34]3[C:42]4[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=4)[NH:36][CH:35]=3)=[CH:5][C:4]=2[N:3]=1

Participants

7

Reactant 4

HCID 5234Sodium ChlorideHCID 10796Cesium carbonateHCID 769243-(2-Bromoethyl)indoleHCID 1363405384-amino-2-ethoxymethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-ol

Product 1

HCID 575452851-(4-amino-2-ethoxymethyl-7-[2-(1H-indol-3-yl)ethoxy]-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-olYield 42.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-Amino-2-ethoxymethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-ol (500 mg, 1.51 mmol), cesium carbonate (980 mg, 3.02 mmol), 3-(2-bromoethyl)indole (375 mg, 1.66 mmol), and DMF (10 mL) were combined and stirred at ambient temperature overnight followed by heating at 80° C. for 4 hours. The reaction mixture was cooled to ambient temperature and poured into 200 mL of water containing 20 g of sodium chloride. The resulting precipitate was filtered, dissolved in dichloromethane, and purified by flash column chromatography on silica gel, eluting with a gradient of 0-8% methanol in dichloromethane. Clean fractions were combined and concentrated. The solid was slurried in hot acetonitrile, filtered, and dried under reduced pressure to yield 305 mg of 1-(4-amino-2-ethoxymethyl-7-[2-(1H-indol-3-yl)ethoxy]-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol as an off-white solid, mp 220.0-222.0° C.

Workup

  1. temperatureby heating at 80° C. for 4 hours
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. filtrationThe resulting precipitate was filtered
  4. dissolutiondissolved in dichloromethane
  5. custompurified by flash column chromatography on silica gel
  6. washeluting with a gradient of 0-8% methanol in dichloromethane
  7. concentrationconcentrated
  8. filtrationfiltered
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-32cda33082714139aa41066becf31938
Source dataset
uspto-grants-2012_09
Patent number
US08263594B2

Reaction notes

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