Acetic Acid → 1-Cyclohexyl-7-{[2-(trimethylsilyl)ethoxy]methyl}-1,2,4,7-tetrahydropyrrolo[3',2':5,6]pyrido[4,3-d][1,3]oxazine

HRID 1506199Notes

Reaction equation

HRID 1506199 reaction equation
[CH:1]1([NH:7][C:8]2[C:13]([CH2:14][OH:15])=[CH:12][N:11]=[C:10]3[N:16]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:17]=[CH:18][C:9]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C=O.[C:29](O)(=O)C.C(=O)([O-])O.[Na+]>C(O)C>[CH:1]1([N:7]2[C:8]3[C:9]4[CH:18]=[CH:17][N:16]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:10]=4[N:11]=[CH:12][C:13]=3[CH2:14][O:15][CH2:29]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 71258447(4-(Cyclohexylamino)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-5-yl)methanol

Product 1

HCID 712583421-Cyclohexyl-7-{[2-(trimethylsilyl)ethoxy]methyl}-1,2,4,7-tetrahydropyrrolo[3',2':5,6]pyrido[4,3-d][1,3]oxazineYield 51%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

[4-(Cyclohexylamino)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-5-yl)methanol (38 mg, 0.10 mmol) and aqueous formaldehyde (35 wt %, 0.6 mL, 8 mmol) in ethanol (2 mL) were stirred at 75° C. for 1 hour. The reaction mixture was then stirred with acetic acid (1 mL) at 75° C. for 1 hour, allowed to cool to room temperature, and after addition of saturated aqueous sodium hydrogen carbonate, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1 (v/v)) to give the title compound as a colorless oil (19.8 mg, yield 51%).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1 (v/v))

Sources & evidence

ORD record
ord-9346d76093cb4e26b54a0eeb167605d0
Source dataset
uspto-grants-2015_12
Patent number
US09216999B2

Reaction notes

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