1,2-Diaminocyclohexane, trans- → 7-(1,1-dioxo-[1,2]thiazinan-2-yl)-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-amine

HRID 909339Notes

Reaction equation

HRID 909339 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.[CH2:27]1[CH2:34][NH:33][S:30](=[O:32])(=[O:31])[CH2:29][CH2:28]1.N[C@@H]1CCCC[C@H]1N.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I.O1CCOCC1>[O:31]=[S:30]1(=[O:32])[CH2:29][CH2:28][CH2:27][CH2:34][N:33]1[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

Participants

7

Reactant 4

HCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 3035081,4-ButanesultamHCID 673820847-Bromo-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-ylamine

Product 1

HCID 116485757-(1,1-dioxo-[1,2]thiazinan-2-yl)-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-amineYield 55.5%

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), 1,4-butanesultam (0.29 g), copper(I) iodide (68 mg), (±)-trans-1,2-diaminocyclohexane (42 μL), potassium phosphate (0.79 g) and dioxane (4 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 at 110° C. for 30 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 polar component of the eluent was chloroform:methanol:ammonium hydroxide 80:18:2 (CMA). The purification was carried out eluting with chloroform:CMA in a gradient from 99:1 to 90:10. Additional purification by recrystallization from acetonitrile provided 0.47 g of 7-(1,1-dioxo-[1,2]thiazinan-2-yl)-2-ethoxymethyl-1-(3-isopropoxypropyl)-1H-imidazo[4,5-c]quinolin-4-amine as pale yellow crystals, mp 172-174° 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-251747851de64646a5506b99436c96ef
Source dataset
uspto-grants-2011_09
Patent number
US08017779B2

Reaction notes

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