Sodium Iodide → 2-methoxymethyl-8-[2-(1-methylpyrrolidin-2-yl)ethoxy]-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

HRID 2203625Notes

Reaction equation

HRID 2203625 reaction equation
C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:9][CH2:10][CH:11]1[CH2:15][CH2:14][CH2:13][N:12]1[CH3:16].[I-].[Na+].[OH:19][C:20]1[CH:29]=[CH:28][C:27]2[N:26]=[C:25]([NH2:30])[C:24]3[N:31]=[C:32]([CH2:37][O:38][CH3:39])[N:33]([CH2:34][CH2:35][CH3:36])[C:23]=3[C:22]=2[CH:21]=1>CC(C)=O>[CH3:39][O:38][CH2:37][C:32]1[N:33]([CH2:34][CH2:35][CH3:36])[C:23]2[C:22]3[CH:21]=[C:20]([O:19][CH2:9][CH2:10][CH:11]4[CH2:15][CH2:14][CH2:13][N:12]4[CH3:16])[CH:29]=[CH:28][C:27]=3[N:26]=[C:25]([NH2:30])[C:24]=2[N:31]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium Carbonate2×HCID 3017050Pyrrolidine, 2-(2-chloroethyl)-1-methyl-, hydrochloride (1:1)2×HCID 68972370HCID 68972370, compound

Product 1

HCID 588336502-methoxymethyl-8-[2-(1-methylpyrrolidin-2-yl)ethoxy]-1-propyl-1H-imidazo[4,5-c]quinolin-4-amineYield 15.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Potassium carbonate (1.48 g, 10.75 mmol), 2-(2-chloroethyl)-1-methylpyrrolidine hydrochloride (483 mg, 2.62 mmol), sodium iodide (100 mg, 0.66 mmol), and 8-hydroxy-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine (500 mg, 1.75 mmol) were combined in acetone and heated at reflux overnight. Additional 2-(2-chloroethyl)-1-methylpyrrolidine hydrochloride and potassium carbonate were added, and the reaction was heated at reflux overnight. The reaction mixture was then cooled to ambient temperature, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on a HORIZON HPFC system (silica cartridge, eluting with a gradient of CMA:chloroform from 0:100 to 25:75) followed by recrystallization from acetonitrile to afford 105 mg of 2-methoxymethyl-8-[2-(1-methylpyrrolidin-2-yl)ethoxy]-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine as an off-white solid, mp 155-157° C. Anal. calcd for C22H31N5O2.0.25H2O: C, 65.66; H, 7.90; N, 17.40. Found: C, 65.66; H, 8.24; N, 17.26.

Workup

  1. temperatureheated
  2. temperatureat reflux overnight
  3. temperaturethe reaction was heated
  4. temperatureat reflux overnight
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography on a HORIZON HPFC system (silica cartridge
  8. washeluting with a gradient of CMA
  9. customchloroform from 0:100 to 25:75) followed by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-f9fd639955394f1d875e038ef8e98907
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

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