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

HRID 242001Notes

Reaction equation

HRID 242001 reaction equation
[N:1]1([C:6]2[CH:28]=[CH:27][C:9]([CH2:10][N:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:14](=S)[C:13]([C:22](OCC)=[O:23])=[N:12]3)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.Cl.[O:30]1[CH2:35][CH2:34][CH2:33][CH:32]([NH:36][NH2:37])[CH2:31]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O.C(#N)C.[Hg](Cl)Cl>[N:1]1([C:6]2[CH:28]=[CH:27][C:9]([CH2:10][N:11]3[C:20]4[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=4[C:14]4=[N:37][N:36]([CH:32]5[CH2:33][CH2:34][CH2:35][O:30][CH2:31]5)[C:22](=[O:23])[C:13]4=[N:12]3)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 66744316(Tetrahydro-2H-pyran-3-yl)hydrazine hydrochlorideHCID 86659984ethyl 1-[4-(1H-pyrazol-1-yl)benzyl]-4-thioxo-1,4-dihydrocinnoline-3-carboxylate

Product 1

HCID 46896615(+/-)-5-[4-(1H-pyrazol-1-yl)benzyl]-2-(tetrahydro-2H-pyran-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one

Reagents, catalysts & solvents 3

HCID 24085Mercuric ChlorideCatalystHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

Ethyl 1-[4-(1H-pyrazol-1-yl)benzyl]-4-thioxo-1,4-dihydrocinnoline-3-carboxylate (200 mg, 0.510 mmol) and (±)-tetrahydro-2H-pyran-3-ylhydrazine hydrochloride (172 mg, 1.13 mmol, 2.2 equiv) were dissolved in N,N-dimethylformamide (10 mL) and acetonitrile (10 mL). The solution was sparged under nitrogen, treated with potassium carbonate (708 mg, 5.12 mmol, 10 equiv) and mercury(II)chloride (139 mg, 0.51 mmol, 1 equiv) and stirred at ambient temperature for 14 hours. The mixture was poured into water and extracted with ethyl acetate (3×70 mL) and 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 0:100; hexanes:ethyl acetate) to provide the titled compound as a dark red solid: 1H-NMR (400 MHz, CDCl3) δ 8.33-8.29 (1H, m), 7.88 (1H, d, J=2.5 Hz), 7.74 (1H, d, J=1.8 Hz), 7.66 (2H, d, J=8.7 Hz), 7.61-7.56 (3H, m), 7.40 (2H, d, J=8.6 Hz), 6.47 (1H, dd, J=2.4, 1.9 Hz), 5.85 (2H, s), 4.77-4.69 (1H, m), 4.06 (1H, ddd, J=10.8, 4.4, 1.6 Hz), 4.00 (1H, d, J=11.0 Hz), 3.84 (1H, ap t, J=10.6 Hz), 3.55-3.48 (1H, m), 2.31-2.19 (1H, m), 2.17-2.10 (1H, m), 1.92-1.83 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 427.1872 [(M+H)+; calculated for C24H22N6O2: 427.1877].

Workup

  1. customThe solution was sparged under nitrogen
  2. extractionextracted with ethyl acetate (3×70 mL)
  3. dry with materialthe combined organic extracts were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-15be1f301edd48b8a20c24914beb533c
Source dataset
uspto-grants-2014_02
Patent number
US08653079B2

Reaction notes

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