Methyl morpholine oxide → 2-(2,3-Dihydroxypropyl)-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

HRID 449942Notes

Reaction equation

HRID 449942 reaction equation
[CH2:1]([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)[CH:2]=C.C[N+]1([O-])CC[O:34]CC1.[C:38](=[O:41])(O)[O-].[Na+]>O1CCCC1.O.[Os](=O)(=O)(=O)=O>[OH:34][CH:2]([CH2:38][OH:41])[CH2:1][N:4]1[C:28](=[O:29])[C:7]2=[N:8][N:9]([CH2:16][C:17]3[CH:18]=[CH:19][C:20]([N:23]4[CH:27]=[CH:26][CH:25]=[N:24]4)=[CH:21][CH:22]=3)[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=3[C:6]2=[N:5]1

Participants

7

Reactant 3

HCID 82029Methyl morpholine oxideHCID 516892Sodium BicarbonateHCID 46897482Allyl-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Product 1

HCID 468965082-(2,3-Dihydroxypropyl)-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Reagents, catalysts & solvents 3

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Allyl-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one [(Example 10), 600 mg, 1.57 mmol] was dissolved in tetrahydrofuran (65 mL) and water (65 mL), treated with 4-methylmorpholine 4-oxide (221 mg, 1.88 mmol, 1.2 equiv) and osmium tetroxide (50.0 μL, 0.160 mmol, 0.1 equiv). The mixture was stirred for 72 hours at ambient temperature, poured into sodium bicarbonate (200 mL, saturated aqueous) and extracted with ethyl acetate (2×150 mL) and chloroform (2×100 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The sodium sulfate was washed with a 1:1 mixture of methanol:chloroform (6×30 mL) and the filtrate was concentrated in vacuo. The residue was purified via silica gel gradient chromatography (100:0 to 85:15; dichloromethane:methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.30-8.26 (1H, m), 7.89 (1H, d, J=2.5 Hz), 7.72-7.67 (3H, m), 7.62-7.54 (3H, m), 7.39 (2H, d, J=8.4 Hz), 6.47-6.45 (1H, m), 5.88 (2H, s), 4.31 (2H, dd, J=5.3, 2.0 Hz), 4.18-4.13 (1H, m), 3.69-3.65 (2H, m), 3.49 (1H, d, J=5.8 Hz), 3.02 (1H, m); high resolution mass spectrometry (ES+) m/z 417.1684 [(M+H)+; calculated for C22H21N6O3: 417.1670].

Workup

  1. extractionextracted with ethyl acetate (2×150 mL) and chloroform (2×100 mL)
  2. dry with materialThe combined organic extracts were dried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. washThe sodium sulfate was washed with a 1:1 mixture of methanol
  6. concentrationchloroform (6×30 mL) and the filtrate was concentrated in vacuo
  7. customThe residue was purified via silica gel gradient chromatography (100:0 to 85:15; dichloromethane:methanol)

Sources & evidence

ORD record
ord-f9c15d08f7ba4c21bfb0420fd6f5173a
Source dataset
uspto-grants-2013_07
Patent number
US08486946B2

Reaction notes

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