m-Chloroperbenzoic acid → (+/-)-2-(Oxiran-2-ylmethyl)-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

HRID 242005Notes

Reaction equation

HRID 242005 reaction equation
ClC1C=C(C(OO)=[O:9])C=CC=1.[CH2:12]([N:15]1[C:39](=[O:40])[C:18]2=[N:19][N:20]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([N:34]4[CH:38]=[CH:37][CH:36]=[N:35]4)=[CH:30][CH:29]=3)[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:26]=3[C:17]2=[N:16]1)[CH:13]=[CH2:14].C(=O)(O)[O-].[Na+]>ClCCl.[Cl-].[Na+].O>[O:9]1[CH2:14][CH:13]1[CH2:12][N:15]1[C:39](=[O:40])[C:18]2=[N:19][N:20]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([N:34]4[CH:38]=[CH:37][CH:36]=[N:35]4)=[CH:30][CH:29]=3)[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:26]=3[C:17]2=[N:16]1

Participants

6

Reactant 3

HCID 70297m-Chloroperbenzoic acid2×HCID 516892Sodium BicarbonateHCID 46897482Allyl-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Product 1

HCID 46896712(+/-)-2-(Oxiran-2-ylmethyl)-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-chlorobenzenecarboperoxoic acid (29 mg, 0.17 mmol, 1.3 equiv) in dichloromethane (3 mL) was cooled to 0° C. and treated with a dichloromethane (1 mL) solution of 2-allyl-5-[4-(1H-pyrazol-1-yl)benzyl]-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one [(Example 10), 50 mg, 0.13 mmol]. After stirring for 1 hour at 0° C., the mixture was warmed to ambient temperature and stirred for an additional 14 hours. The mixture was treated with additional 3-chlorobenzenecarboperoxoic acid (50.0 mg, 0.29 mmol, 2.2 equiv) and after three hours, the mixture was cooled to 0° C., treated with sodium bicarbonate (3 mL, saturated aqueous), diluted with brine (10 mL) and extracted with dichloromethane (3×30 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified via silica gel gradient chromatography (0:100 to 100:0; hexanes:ethyl acetate), providing the titled compound as a dark red solid: 1H-NMR (400 MHz, CDCl3) δ 8.31-8.28 (1H, m), 7.89 (1H, d, J=2.5 Hz), 7.71 (1H, d, J=1.4 Hz), 7.68 (2H, d, J=8.7 Hz), 7.57-7.51 (3H, m), 7.38 (2H, d, J=8.7 Hz), 6.46 (1H, dd, J=2.4, 1.8 Hz), 5.85 (2H, s), 4.32 (1H, dd, J=14.5, 4.5 Hz), 4.22 (1H, dd, J=14.5, 5.5 Hz), 3.43-3.38 (1H, m), 2.88 (1H, dd, J=4.7, 4.1 Hz), 2.79 (1H, dd, J=4.8, 2.6 Hz) ppm. high resolution mass spectrometry (ES+) m/z 399.1563 [(M+H)+; calculated for C22H18N6O2: 399.1564].

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. extractionextracted with dichloromethane (3×30 mL)
  5. dry with materialThe combined organic extracts were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified via silica gel gradient chromatography (0:100 to 100:0; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-6c4e8035c7a14d33860c0eabe28a4f6a
Source dataset
uspto-grants-2014_02
Patent number
US08653079B2

Reaction notes

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