Water → HCID 52914157, compound

HRID 341034Notes

Reaction equation

HRID 341034 reaction equation
[C:1]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[C:11]3=[N:18][NH:19][C:20](=[O:21])[C:10]3=[CH:9]2)=[CH:3][CH:2]=1.[H-].[Na+].[CH2:30](Br)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.O>CN(C)C=O>[C:1]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:2]=[CH:3][C:4]([CH2:7][N:8]2[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[C:11]3=[N:18][N:19]([CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:20](=[O:21])[C:10]3=[CH:9]2)=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 68154431HCID 68154431, compound

Product 1

HCID 52914157HCID 52914157, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

5-Biphenyl-4-ylmethyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one [(Example 8, Step 3), 110 mg, 0.313 mmol] was dissolved in N,N-dimethylformamide (5 mL), cooled to 0° C. and treated with sodium hydride (37.6 mg, 0.939 mmol, 3 equiv). After stirring for 15 minutes, the mixture was warmed to ambient temperature and stirred for an additional 15 minutes. The mixture was cooled to 0° C., treated with benzyl bromide (0.112 mL, 0.939 mmol, 3 equiv) and after 5 minutes, was warmed to ambient temperature over 2 hours and stirred for an additional 14 hours at ambient temperature. The mixture was poured into water (40 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 95:5; dichloromethane:methanol), providing the titled compound: high resolution mass spectrometry (ES+) m/z 442.1922 [(M+H)+; calculated for C30H24N3O: 442.1914].

Workup

  1. temperaturethe mixture was warmed to ambient temperature
  2. stirringstirred for an additional 15 minutes
  3. temperatureThe mixture was cooled to 0° C.
  4. temperaturewas warmed to ambient temperature over 2 hours
  5. stirringstirred for an additional 14 hours at ambient temperature
  6. extractionextracted with ethyl acetate (2×50 mL)
  7. dry with materialThe combined organic extracts were dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel gradient chromatography (100:0 to 95:5; dichloromethane:methanol)

Sources & evidence

ORD record
ord-22ddc66ab6e84ac49f5c117f8ae619b6
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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