Pyrazole → (+/-)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2-(tetrahydro-2H-pyran-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one

HRID 2067118Notes

Reaction equation

HRID 2067118 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:14]3[N:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12]3=[N:19][N:20]([CH:23]4[CH2:28][CH2:27][CH2:26][O:25][CH2:24]4)[C:21](=[O:22])[C:11]3=[N:10]2)=[CH:4][CH:3]=1.[NH:29]1[CH:33]=[CH:32][CH:31]=[N:30]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CN[C@@H]1CCCC[C@H]1NC.C(=O)(O)[O-].[Na+]>CN(C)C=O.[Cu]I>[N:29]1([C:2]2[CH:7]=[CH:6][C:5]([CH2:8][N:9]3[C:14]4[N:15]=[CH:16][CH:17]=[CH:18][C:13]=4[C:12]4=[N:19][N:20]([CH:23]5[CH2:28][CH2:27][CH2:26][O:25][CH2:24]5)[C:21](=[O:22])[C:11]4=[N:10]3)=[CH:4][CH:3]=2)[CH:33]=[CH:32][CH:31]=[N:30]1

Participants

8

Reactant 5

HCID 1048PyrazoleHCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 66744325(+/-)-5-[(4-iodophenyl)methyl]-2-(tetrahydro-2H-pyran-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one

Product 1

HCID 49763460(+/-)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2-(tetrahydro-2H-pyran-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

(±)-5-[(4-Iodophenyl)methyl]-2-(tetrahydro-2H-pyran-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one (50 mg, 0.10 mmol), pyrazole (11 mg, 0.17 mmol, 1.7 equiv), potassium phosphate (71 mg, 0.41 mmol, 4 equiv), (±)-trans-N,N′-dimethylcyclohexane-1,2-diamine (44 mg, 0.31 mmol, 3 equiv) and copper(I) iodide (20 mg, 0.10 mmol, 1 equiv) were combined in degassed N,N-dimethylformamide (2 mL) and placed into a preheated oil bath at 110° C. for 1 hour. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (25 mL, aqueous saturated) 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 by silica gel gradient chromatography (100:0 to 95:5 dichloromethane:methanol), providing the titled compound as a red solid: 1H-NMR (400 MHz, CDCl3) δ 8.74 (1H, dd, J=4.5, 1.7 Hz), 8.51 (1H, dd, J=8.0, 1.8 Hz), 8.78 (1H, d, J=2.5 Hz), 7.69 (1H, d, J=1.7 Hz), 7.64-7.62 (4H, m), 7.49 (1H, dd, J=8.0, 4.6 Hz), 6.44 (1H, dd, J=2.5, 1.6 Hz), 5.95 (2H, br s), 4.71-4.63 (1H, m), 4.01-3.95 (2H, m), 3.74 (1H, ap t, J=10.5 Hz), 3.47 (1H, td, J=11.1, 3.6 Hz), 2.22-2.06 (2H, m), 1.92-1.79 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 428.1837 [(M+H)+; calculated for C23H22N7O2:428.1829].

Workup

  1. extractionextracted with ethyl acetate (3×50 mL)
  2. dry with materialThe combined organic extracts were dried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel gradient chromatography (100:0 to 95:5 dichloromethane:methanol)

Sources & evidence

ORD record
ord-20a7dd0f5bb5407bb3a9e9f6870c69d1
Source dataset
uspto-grants-2012_10
Patent number
US08293744B2

Reaction notes

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