Methanol → (+/-)-2-(2,3-dimethoxypropyl)-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

HRID 449969Notes

Reaction equation

HRID 449969 reaction equation
O[CH:2]([CH2:30][OH:31])[CH2:3][N:4]1[C:28](=[O:29])[C:7]2=[N:8][N:9]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH:27]=[CH:26][CH:25]=[N:24]4)=[CH:19][CH:18]=3)[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=3[C:6]2=[N:5]1.[H-].[Na+].IC.[CH3:36][OH:37].[CH3:38]N(C)C=O>O>[CH3:36][O:37][CH:2]([CH2:30][O:31][CH3:38])[CH2:3][N:4]1[C:28](=[O:29])[C:7]2=[N:8][N:9]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]4[CH:27]=[CH:26][CH:25]=[N:24]4)=[CH:19][CH:18]=3)[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=3[C:6]2=[N:5]1

Participants

7

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 468965082-(2,3-Dihydroxypropyl)-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Product 1

HCID 46896713(+/-)-2-(2,3-dimethoxypropyl)-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

(±)-2-(2,3-Dihydroxypropyl)-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one [(Example 11), 0.10 g, 0.24 mmol] was dissolved in degassed N,N-dimethylformamide (5 mL), cooled to 0° C. and sparged under nitrogen. The mixture was treated with sodium hydride (21 mg, 0.53 mmol, 2.2 equiv) and after minutes, treated with iodomethane (37 μL, 0.60 mmol, 2.5 equiv). After stirring for 1 hour, the mixture was treated with methanol (2 mL), poured into water (25 mL) and extracted with ethyl acetate (3×50 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 0:100; hexanes:ethyl acetate containing 10% methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.29-8.26 (1H, m), 7.89 (1H, d, J=2.5 Hz), 7.71 (1H, d, J=1.7 Hz), 7.68 (2H, d, J=8.6 Hz), 7.56-7.51 (3H, m), 7.39 (2H, d, J=8.6 Hz), 6.46 (1H, dd, J=2.4, 1.9 Hz), 5.83 (2H, s), 4.21 (2H, d, J=5.8 Hz), 3.92-3.86 (1H, m), 3.64 (1H, dd, J=10.4, 3.7 Hz), 3.55 (1H, dd, J=10.4, 6.0 Hz), 3.52 (3H, s), 3.42 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 445.1976 [(M+H)+; calculated for C24H24N6O3: 445.1983].

Workup

  1. customsparged under nitrogen
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organic extracts were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified via silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate containing 10% methanol)

Sources & evidence

ORD record
ord-527beeef382d449784f6c33060d21c47
Source dataset
uspto-grants-2013_07
Patent number
US08486946B2

Reaction notes

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