Dimethylformamide dimethyl acetal → 9-Cyclohexyl-3-{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-h][1,6]naphthyridin-6(9H)-one

HRID 1506228Notes

Reaction equation

HRID 1506228 reaction equation
[CH:1]1([NH:7][C:8]2[C:13]([C:14](=[O:16])[CH3:15])=[CH:12][N:11]=[C:10]3[N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[CH:18]=[N:19][C:9]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:28]OC(OC)N(C)C>>[CH:1]1([N:7]2[C:8]3[C:9]4[N:19]=[CH:18][N:17]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:26])([CH3:25])[CH3:27])[C:10]=4[N:11]=[CH:12][C:13]=3[C:14](=[O:16])[CH:15]=[CH:28]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

3

Reactant 2

HCID 78373Dimethylformamide dimethyl acetalHCID 712584381-[7-(Cyclohexylamino)-3-{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-b]pyridin-6-yl]ethanone

Product 1

HCID 712582749-Cyclohexyl-3-{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-h][1,6]naphthyridin-6(9H)-oneYield 63%

Procedure

1-[7-(Cyclohexylamino)-3-{[2-(trimethylsilyl)ethoxy]methyl}-3H-imidazo[4,5-b]pyridin-6-yl]ethanone (88.9 mg, 0.229 mmol) in N,N-dimethylformamide dimethyl acetal (2.0 mL) was stirred at 180° C. for 5 hours. The reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure, and the resulting residue was dissolved in tetrahydrofuran (5 mL) and stirred with 1 M hydrochloric acid (2 mL) at 80° C. for 1 hour. The reaction mixture was allowed to cool to room temperature and, after addition of saturated aqueous sodium hydrogen carbonate, extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate/methanol=1/1/0→0/10/1 (v/v/v)) to give the title compound as a yellow solid (57.5 mg, yield 63%).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionthe resulting residue was dissolved in tetrahydrofuran (5 mL)
  3. temperatureto cool to room temperature
  4. additionafter addition of saturated aqueous sodium hydrogen carbonate
  5. extractionextracted with ethyl acetate
  6. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate/methanol=1/1/0→0/10/1 (v/v/v))

Sources & evidence

ORD record
ord-6c589b1ab59b4a35bf9f23e5d2588b20
Source dataset
uspto-grants-2015_12
Patent number
US09216999B2

Reaction notes

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