Cesium carbonate → 1-[2-ethoxymethyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-7-yl]pyrrolidin-2-one

HRID 909358Notes

Reaction equation

HRID 909358 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[C:6]3[N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:13]([CH2:19][O:20][CH2:21][CH3:22])=[N:12][C:7]=3[CH:8]=[N:9][C:10]=2[CH:11]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[NH:71]1[CH2:75][CH2:74][CH2:73][C:72]1=[O:76]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH2:21]([O:20][CH2:19][C:13]1[N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:6]2[C:5]3[N:4]=[CH:3][C:2]([N:71]4[CH2:75][CH2:74][CH2:73][C:72]4=[O:76])=[CH:11][C:10]=3[N:9]=[CH:8][C:7]=2[N:12]=1)[CH3:22]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 120252-PyrrolidoneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 670524337-bromo-2-(ethoxymethyl)-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridine

Product 1

HCID 673821111-[2-ethoxymethyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-7-yl]pyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

7-Bromo-2-(ethoxymethyl)-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridine (1.0 g, 2.75 mmol), tris(dibenzylideneacetone)dipalladium(0) (70 mg, 0.068 mmol), cesium carbonate (1.25 g, 3.85 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.118 g, 0.204 mmol), pyrrolidin-2-one (0.25 mL, 3.3 mmol), and dioxane (2.75 mL) were added to a scintillation vial. The vial was sequentially flushed with nitrogen, sealed with a Teflon-lined cap, and heated at 110° C. for about 40 hours. After cooling to room temperature, the reaction mixture was diluted with chloroform and methanol and then filtered through CELITE filter aid. The filtrate was concentrated under reduced pressure to provide a tan solid. This material was purified by column chromatography on a Biotage Horizon™ High-Performance Flash Chromatography instrument using a silica gel cartridge and eluting with a gradient of 1-25% CMA in chloroform to provide 1-[2-ethoxymethyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-7-yl]pyrrolidin-2-one.

Workup

  1. customThe vial was sequentially flushed with nitrogen
  2. customsealed with a Teflon-
  3. customlined cap
  4. temperatureAfter cooling to room temperature
  5. additionthe reaction mixture was diluted with chloroform and methanol
  6. filtrationfiltered through CELITE
  7. filtrationfilter aid
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customto provide a tan solid
  10. customThis material was purified by column chromatography on a Biotage Horizon™ High-Performance Flash Chromatography instrument
  11. washeluting with a gradient of 1-25% CMA in chloroform

Sources & evidence

ORD record
ord-c2245be519f842e98942d2246c68d8b5
Source dataset
uspto-grants-2011_09
Patent number
US08017779B2

Reaction notes

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