Methane → tert-butyl 2-{2-[2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethoxy}ethyl(methyl)carbamate

HRID 1826170Notes

Reaction equation

HRID 1826170 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[NH:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][N:18]([CH3:26])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:9][CH:8]=[CH:7][CH:6]=2.C(N(CC)CC)C.[CH3:34][O:35][CH2:36][CH2:37][C:38](Cl)=O.C>C(Cl)Cl.CCO.CO>[CH3:34][O:35][CH2:36][CH2:37][C:38]1[N:12]([CH2:13][CH2:14][O:15][CH2:16][CH2:17][N:18]([CH3:26])[C:19](=[O:25])[O:20][C:21]([CH3:22])([CH3:23])[CH3:24])[C:11]2[C:10]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:4]=[CH:3][C:2]=2[N:1]=1

Participants

8

Reactant 4

HCID 297MethaneHCID 8471Triethylamine2×HCID 27597283-Methoxypropanoyl chlorideHCID 69011088Tert-butyl 2-{2-[(3-aminoquinolin-4-yl)amino]ethoxy}ethyl(methyl)carbamate

Product 1

HCID 21898022tert-butyl 2-{2-[2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethoxy}ethyl(methyl)carbamateYield 100%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of tert-butyl 2-{2-[(3-aminoquinolin-4-yl)amino]ethoxy}ethyl(methyl)carbamate (6.05 g, 16.8 mmol) in 200 mL of anhydrous CH2Cl2 was cooled to 0° C. and treated with triethylamine (2.40 mL, 17.2 mmol). Methoxypropionyl chloride (1.72 mL, 17.2 mmol) was then added dropwise over 5 min. The reaction was then warmed to room temperature and stirring was continued for 3 h. The reaction mixture was then concentrated under reduced pressure to give an orange solid. This was dissolved in 200 mL of EtOH and 7.2 mL of triethylamine was added. The mixture was heated to reflux and stirred under N2 overnight. The reaction was then concentrated to dryness under reduced pressure and treated with 300 mL of Et2O. The mixture was then filtered and the filtrate was concentrated under reduced pressure to give a brown solid. This was dissolved in 300 mL of CH2Cl2 and washed with H2O and brine. The organic portion was dried over Na2SO4 and concentrated under reduced pressure to give a brown oil. The oil was dissolved in 100 mL of hot MeOH and treated with activated charcoal. The hot solution was filtered and concentrated to give 7.20 g of tert-butyl 2-{2-[2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]ethoxy}ethyl(methyl)carbamate as a yellow syrup.

Workup

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. customto give an orange solid
  3. temperatureThe mixture was heated
  4. temperatureto reflux
  5. stirringstirred under N2 overnight
  6. concentrationThe reaction was then concentrated to dryness under reduced pressure
  7. additiontreated with 300 mL of Et2O
  8. filtrationThe mixture was then filtered
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customto give a brown solid
  11. washwashed with H2O and brine
  12. dry with materialThe organic portion was dried over Na2SO4
  13. concentrationconcentrated under reduced pressure
  14. customto give a brown oil
  15. filtrationThe hot solution was filtered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-38b4e2dae389465a93ce3d83b0334829
Source dataset
uspto-grants-2006_05
Patent number
US07049439B2

Reaction notes

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