Cesium carbonate → 2-(2,3-dimethylphenyl)-5-[(6'-methyl-2,3'-bipyridin-5-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one

HRID 2067107Notes

Reaction equation

HRID 2067107 reaction equation
Cl[C:2]1[N: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]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[C:24]=4[CH3:30])[C:21](=[O:22])[C:11]3=[N:10]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:37][C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][N:39]=1.C(=O)(O)[O-].[Na+]>O1CCCC1.[Cu]Cl.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.O>[CH3:30][C:24]1[C:25]([CH3:29])=[CH:26][CH:27]=[CH:28][C:23]=1[N:20]1[C:21](=[O:22])[C:11]2=[N:10][N:9]([CH2:8][C:5]3[CH:4]=[CH:3][C:2]([C:41]4[CH:40]=[N:39][C:38]([CH3:37])=[CH:43][CH:42]=4)=[N:7][CH:6]=3)[C:14]3[N:15]=[CH:16][CH:17]=[CH:18][C:13]=3[C:12]2=[N:19]1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 27630812-Methylpyridine-5-boronic acidHCID 497633445-[(6-chloropyridin-3-yl)methyl]-2-(2,3-dimethylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one

Product 1

HCID 497633452-(2,3-dimethylphenyl)-5-[(6'-methyl-2,3'-bipyridin-5-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-[(6-Chloropyridin-3-yl)methyl]-2-(2,3-dimethylphenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one [(Example 4), 47 mg, 0.11 mmol], cesium carbonate (92 mg, 0.28 mmol, 2.5 equiv), copper(I) chloride (11 mg, 0.11 mmol, 1 equiv), 2-methyl-5-pyridinylboronic acid (39 mg, 0.28 mmol, 2.5 equiv) and bis(tri-tert-butylphosphine)palladium(0) (11 mg, 0.023 mmol, 0.2 equiv) were combined in tetrahydrofuran (4 mL) and placed into a preheated oil bath at 70° C. After 45 minutes, water (1 mL) was added and after 45 minutes, the mixture was poured into sodium bicarbonate (50 mL) and extracted with ethyl acetate (2×50 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 0:100; hexanes:ethyl acetate containing 5% methanol), providing the titled compound as a deep red solid: 1H-NMR (400 MHz, CDCl3) δ 9.04 (1H, d, J=1.4 Hz), 8.89 (1H, d, J=2.3 Hz), 8.79 (1H, dd, J=4,6, 1.7 Hz), 8.55 (1H, dd, J=8.0, 1.8 Hz), 8.18 (1H, dd, J=8.1, 2.3 Hz), 8.03 (1H, dd, J=8.2, 2.2 Hz), 7.70 (1H, d, J=8.2 Hz), 7.52 (1H, dd, J=8.0, 4.6 Hz), 7.27-7.25 (1H, m), 7.24-7.22 (3H, m), 6.02 (2H, s), 2.61 (3H, s), 2.36 (3H, s), 2.16 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 474.2043 [(M+H)+; calculated for C28H24N7O: 474.2037].

Workup

  1. customplaced into a preheated oil bath at 70° C
  2. extractionextracted with ethyl acetate (2×50 mL)
  3. dry with materialThe combined organic extracts were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate containing 5% methanol)

Sources & evidence

ORD record
ord-652f3ce6d964431fac44874ddf353654
Source dataset
uspto-grants-2012_10
Patent number
US08293744B2

Reaction notes

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