3-Pyridinemethanol → 2-ethoxymethyl-5-oxido-1-propyl-8-(pyridin-3-ylmethoxy)-1H-imidazo[4,5-c]quinoline

HRID 2383182Notes

Reaction equation

HRID 2383182 reaction equation
[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:19][CH2:20][CH3:21])[C:7]2[C:16]3[CH:15]=[C:14]([OH:17])[CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:18]=1)[CH3:2].C1C=C(Cl)C=C(C(OO)=[O:30])C=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:52]1[CH:57]=[CH:56][CH:55]=[C:54]([CH2:58]O)[CH:53]=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>ClCCl.C1COCC1.O>[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:19][CH2:20][CH3:21])[C:7]2[C:16]3[CH:15]=[C:14]([O:17][CH2:58][C:54]4[CH:53]=[N:52][CH:57]=[CH:56][CH:55]=4)[CH:13]=[CH:12][C:11]=3[N+:10]([O-:30])=[CH:9][C:8]=2[N:18]=1)[CH3:2]

Participants

9

Reactant 5

HCID 75103-Pyridinemethanol2×HCID 11776Triphenylphosphine2×HCID 70297m-Chloroperbenzoic acidHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 670510882-ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Ethoxymethyl-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol (680 mg, 2.38 mmol) was dissolved in dichloromethane and mCPBA (60%, 750 mg, 2.62 mmol) was added. The reaction was monitored by TLC and when all of the starting material was determined to be consumed, 20 mL of 2% aqueous sodium carbonate was added. The organic layer was extracted with 2 additional portions of 2% sodium carbonate. The aqueous fractions were combined and concentrated hydrochloric acid was added dropwise until the pH reached 1. The pH was then adjusted to 5 with the portionwise addition of 2% sodium carbonate. A precipitate formed and was collected by filtration to give crude 2-ethoxymethyl-5-oxido-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol as an off-white powder. The solid was combined in 50 mL of anhydrous THF with triphenylphosphine (1.2 g, 4.76 mmol) and pyridine-3-methanol (390 mg, 3.57 mmol). Diisopropyl azodicarboxylate (1.2 g, 5.95 mmol) was added dropwise. After 4 hours, additional portions of triphenyphosphine and pyridine-3-methanol followed by diisopropyldicarboxylate were added and the reaction was stirred for one hour. Water (1 mL) was added and the reaction stirred overnight. The reaction mixture was concentrated under reduced pressure and the resulting solid was dissolved in dichloromethane and washed 3 times with 50 mL portions of 2% aqueous sodium carbonate. The aqueous fractions were combined and extracted with chloroform. The organic fractions were combined, dried over magnesium sulfate, filtered, and concentrated to give crude 2-ethoxymethyl-5-oxido-1-propyl-8-(pyridin-3-ylmethoxy)-1H-imidazo[4,5-c]quinoline.

Workup

  1. customto be consumed
  2. addition20 mL of 2% aqueous sodium carbonate was added
  3. extractionThe organic layer was extracted with 2 additional portions of 2% sodium carbonate
  4. additionconcentrated hydrochloric acid was added dropwise until the pH
  5. additionThe pH was then adjusted to 5 with the portionwise addition of 2% sodium carbonate
  6. customA precipitate formed
  7. filtrationwas collected by filtration
  8. customto give crude 2-ethoxymethyl-5-oxido-1-propyl-1H-imidazo[4,5-c]quinolin-8-ol as an off-white powder
  9. additionwere added
  10. stirringthe reaction stirred overnight
  11. concentrationThe reaction mixture was concentrated under reduced pressure
  12. dissolutionthe resulting solid was dissolved in dichloromethane
  13. washwashed 3 times with 50 mL portions of 2% aqueous sodium carbonate
  14. extractionextracted with chloroform
  15. dry with materialdried over magnesium sulfate
  16. filtrationfiltered
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-ce2591dfa38d43b28b2e5e91fa74d560
Source dataset
uspto-grants-2012_09
Patent number
US08263594B2

Reaction notes

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