Trichloroacetyl isocyanate → 2-ethoxymethyl-1-propyl-8-(pyridin-3-ylmethoxy)-1H-imidazo[4,5-c]quinolin-4-amine

HRID 2383183Notes

Reaction equation

HRID 2383183 reaction equation
[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:27][CH2:28][CH3:29])[C:7]2[C:16]3[CH:15]=[C:14]([O:17][CH2:18][C:19]4[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=4)[CH:13]=[CH:12][C:11]=3[N+:10]([O-])=[CH:9][C:8]=2[N:26]=1)[CH3:2].ClC(Cl)(Cl)C([N:34]=C=O)=O>ClCCl>[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:27][CH2:28][CH3:29])[C:7]2[C:16]3[CH:15]=[C:14]([O:17][CH2:18][C:19]4[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=4)[CH:13]=[CH:12][C:11]=3[N:10]=[C:9]([NH2:34])[C:8]=2[N:26]=1)[CH3:2]

Participants

4

Reactant 2

HCID 76400Trichloroacetyl isocyanateHCID 670509972-ethoxymethyl-5-oxido-1-propyl-8-(pyridin-3-ylmethoxy)-1H-imidazo[4,5-c]quinoline

Product 1

HCID 575452912-ethoxymethyl-1-propyl-8-(pyridin-3-ylmethoxy)-1H-imidazo[4,5-c]quinolin-4-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The crude 2-ethoxymethyl-5-oxido-1-propyl-8-(pyridin-3-ylmethoxy)-1H-imidazo[4,5-c]quinoline from Part A was dissolved in 50 mL of dichloromethane and trichloroacetyl isocyanate (540 mg, 2.85 mmol) was added dropwise. The reaction was monitored by thin layer chromatography and once the starting material was consumed, 2 mL of concentrated ammonium hydroxide was added. The reaction was stirred for 30 minutes and then passed through a column containing cation-exchange resin. The column was washed with methanol to remove impurities followed by elution of the desired product from the column with 2M ammonia in methanol. The volatiles were removed under reduced pressure. The resulting residue was dissolved in dichloromethane and purified by column chromatography on a HORIZON HPFC system. A silica gel cartridge was used eluting with a gradient of 0-8% methanol in dichloromethane. The solid was further purified by recrystallization from acetonitrile to give 2-ethoxymethyl-1-propyl-8-(pyridin-3-ylmethoxy)-1H-imidazo[4,5-c]quinolin-4-amine as light amber crystals, mp 190.0-191.0° C.

Workup

  1. customonce the starting material was consumed
  2. addition2 mL of concentrated ammonium hydroxide was added
  3. additioncontaining cation-exchange resin
  4. washThe column was washed with methanol
  5. customto remove impurities
  6. washfollowed by elution of the desired product from the column with 2M ammonia in methanol
  7. customThe volatiles were removed under reduced pressure
  8. dissolutionThe resulting residue was dissolved in dichloromethane
  9. custompurified by column chromatography on a HORIZON HPFC system
  10. washA silica gel cartridge was used eluting with a gradient of 0-8% methanol in dichloromethane
  11. customThe solid was further purified by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-875cb917606347e18ac55f0d6acd0ee6
Source dataset
uspto-grants-2012_09
Patent number
US08263594B2

Reaction notes

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