Methanol → HCID 178515272, compound

HRID 2067120Notes

Reaction equation

HRID 2067120 reaction equation
C[O:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][N:16]3[C:21]4[N:22]=[CH:23][CH:24]=[CH:25][C:20]=4[C:19]4=[N:26][N:27]([CH:30]5[CH2:35][CH2:34][CH2:33][O:32][CH2:31]5)[C:28](=[O:29])[C:18]4=[N:17]3)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.I[Si](C)(C)C.CO.O>ClCCl>[OH:2][C:3]1[N:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12]([CH2:15][N:16]3[C:21]4[N:22]=[CH:23][CH:24]=[CH:25][C:20]=4[C:19]4=[N:26][N:27]([CH:30]5[CH2:35][CH2:34][CH2:33][O:32][CH2:31]5)[C:28](=[O:29])[C:18]4=[N:17]3)=[CH:13][CH:14]=2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 85247Trimethylsilyl iodide2×HCID 49764834HCID 49764834, compound

Product 1

HCID 178515272HCID 178515272, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(±)-5-({4-[6-(Methyloxy)pyridin-3-yl]phenyl}methyl)-2-(tetrahydro-2H-pyran-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one (Example 14, 20 mg, 0.043 mmol) was dissolved in dichloromethane (3 mL), cooled to 0° C. and treated with iodotrimethylsilane (26 μL, 0.13 mmol, 3 equiv). After stirring for 15 minutes at 0° C., the mixture was warmed to ambient temperature and stirred for an additional 14 hours. The mixture was cooled to 0° C. treated with additional iodotrimethylsilane (26 μL, 0.13 mmol, 3 equiv) and after stirring for 15 minutes at 0° C., the mixture was warmed to ambient temperature and stirred for an additional 14 hours. The mixture was treated with methanol (1 mL), poured into water (10 mL) and extracted with ethyl acetate (2×20 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified via silica gel gradient chromatography (100:0 to 90: 10; dichloromethane:methanol), providing the titled compound as a deep red solid: high resolution mass spectrometry (ES+) m/z 455.1839 [(M+H)+; calculated for C25H23N6O3: 455.1826].

Workup

  1. temperaturethe mixture was warmed to ambient temperature
  2. stirringstirred for an additional 14 hours
  3. temperatureThe mixture was cooled to 0° C.
  4. stirringafter stirring for 15 minutes at 0° C.
  5. temperaturethe mixture was warmed to ambient temperature
  6. stirringstirred for an additional 14 hours
  7. extractionextracted with ethyl acetate (2×20 mL)
  8. dry with materialThe combined organic extracts were dried with sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified via silica gel gradient chromatography (100:0 to 90: 10; dichloromethane:methanol)

Sources & evidence

ORD record
ord-bfb836f5bbc14ff693be769f5dfb1a96
Source dataset
uspto-grants-2012_10
Patent number
US08293744B2

Reaction notes

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