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

HRID 2203614Notes

Reaction equation

HRID 2203614 reaction equation
C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:9][CH2:10][N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.[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.ClCCl>[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][N:11]4[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]4)[CH:29]=[CH:28][C:27]=3[N:26]=[C:25]([NH2:30])[C:24]=2[N:31]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 74826Piperidine, 1-(2-chloroethyl)-, hydrochlorideHCID 689723708-hydroxy-2-methoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine

Product 1

HCID 588337402-methoxymethyl-8-(2-piperidin-1-ylethoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amineYield 25.2%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 6344DichloromethaneSolvent

Procedure

Potassium carbonate (1.48 g, 10.75 mmol), N-(2-chloroethyl)-piperidine 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 as a slurry and heated at reflux overnight. The reaction mixture was cooled to ambient temperature and filtered. The filter cake was washed with acetone and the combined filtrate was concentrated under reduced pressure to afford a solid. The solid material was dissolved in dichloromethane and purified by chromatography on a HORIZON HPFC system (eluting with a gradient of CMA:chloroform from 0:100 to 40:60). The resulting material was concentrated under reduced pressure and crystallized from acetonitrile to afford 175 mg of 2-methoxymethyl-8-(2-piperidin-1-ylethoxy)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine as tan crystals, mp 160-162° C. Anal. calcd for C22H31N5O2.0.33 CH3CN.0.33H2O: C, 65.18; H, 7.90; N, 17.82. Found: C, 65.18; H, 8.05; N, 18.10.

Workup

  1. temperatureheated
  2. temperatureat reflux overnight
  3. filtrationfiltered
  4. washThe filter cake was washed with acetone
  5. concentrationthe combined filtrate was concentrated under reduced pressure
  6. customto afford a solid
  7. custompurified by chromatography on a HORIZON HPFC system (
  8. washeluting with a gradient of CMA
  9. concentrationThe resulting material was concentrated under reduced pressure
  10. customcrystallized from acetonitrile

Sources & evidence

ORD record
ord-8d8bee95ac9846d689efd6f285c16aee
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

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