N,N'-Dimethylethylenediamine → 1-[4-amino-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-7-yl]-1H-pyridin-2-one

HRID 909346Notes

Reaction equation

HRID 909346 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:15]([CH2:16][CH2:17][CH2:18][O:19][CH:20]([CH3:22])[CH3:21])[C:14]([CH2:23][O:24][CH2:25][CH3:26])=[N:13][C:7]=3[C:8]([NH2:12])=[N:9][C:10]=2[CH:11]=1.[NH:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]1=[O:33].CNCCNC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I.O1CCOCC1>[NH2:12][C:8]1[C:7]2[N:13]=[C:14]([CH2:23][O:24][CH2:25][CH3:26])[N:15]([CH2:16][CH2:17][CH2:18][O:19][CH:20]([CH3:22])[CH3:21])[C:6]=2[C:5]2[CH:4]=[CH:3][C:2]([N:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]3=[O:33])=[CH:11][C:10]=2[N:9]=1

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 88712-PyridoneHCID 62657Potassium Phosphate, TribasicHCID 673820847-Bromo-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-ylamine

Product 1

HCID 589675241-[4-amino-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-7-yl]-1H-pyridin-2-oneYield 49%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

7-Bromo-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-amine (0.75 g), 2(1H)-pyridone (0.20 g), copper(I) iodide (68 mg), N,N′-dimethylethylenediamine (75 μL), potassium phosphate (0.79 g) and dioxane (2.7 mL) were added to a scintillation vial. The vial was flushed with nitrogen, sealed with a Teflon-lined cap, placed in an oil bath, and heated to 110° C. for 60 hours. The reaction was cooled to ambient temperature, diluted with chloroform and filtered through a bed of CELITE filter agent. The solvent was evaporated and the residue was purified by column chromatography on a Biotage Horizon™ High-Performance Flash Chromatography instrument using a silica gel cartridge. The purification was carried out eluting with chloroform:CMA in a gradient from 99:1 to 75:25. Additional purification by recrystallization from acetonitrile provided 0.38 g of 1-[4-amino-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-7-yl]-1H-pyridin-2-one as a tan solid, mp 161-163.5° C.

Workup

  1. customThe vial was flushed with nitrogen
  2. customsealed with a Teflon-
  3. customlined cap
  4. customplaced in an oil bath
  5. temperatureThe reaction was cooled to ambient temperature
  6. additiondiluted with chloroform
  7. filtrationfiltered through a bed of CELITE
  8. filtrationfilter agent
  9. customThe solvent was evaporated
  10. customthe residue was purified by column chromatography on a Biotage Horizon™ High-Performance Flash Chromatography instrument
  11. customThe purification
  12. washwas carried out eluting with chloroform
  13. customAdditional purification
  14. customby recrystallization from acetonitrile

Sources & evidence

ORD record
ord-fe06b0af90f045d88051afe5b3b469fd
Source dataset
uspto-grants-2011_09
Patent number
US08017779B2

Reaction notes

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