Water → HCID 49763578, compound

HRID 2067128Notes

Reaction equation

HRID 2067128 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:14]3[CH:15]=[CH:16][S:17][C:13]=3[C:12]3=[N:18][N:19]([CH:22]4[CH2:27][CH2:26][CH2:25][O:24][CH2:23]4)[C:20](=[O:21])[C:11]3=[N:10]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:34][C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][N:36]=1.O>CN(C)C=O.[Cu]Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:34][C:35]1[N:36]=[CH:37][C:38]([C:2]2[CH:7]=[CH:6][C:5]([CH2:8][N:9]3[C:14]4[CH:15]=[CH:16][S:17][C:13]=4[C:12]4=[N:18][N:19]([CH:22]5[CH2:27][CH2:26][CH2:25][O:24][CH2:23]5)[C:20](=[O:21])[C:11]4=[N:10]3)=[CH:4][CH:3]=2)=[CH:39][CH:40]=1

Participants

9

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27630812-Methylpyridine-5-boronic acidHCID 66745523HCID 66745523, compound

Product 1

HCID 49763578HCID 49763578, compound

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Procedure

(±)-5-[(4-Iodophenyl)methyl]-2-(tetrahydro-2H-pyran-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]thieno[2,3-e]pyridazin-3-one (50 mg, 0.10 mmol), cesium carbonate (66 mg, 0.20 mmol, 2 equiv), copper(I) chloride (10 mg, 0.10 mmol, 1 equiv), 2-methyl-5-pyridinylboronic acid (22 mg, 0.14 mmol, 1.4 equiv), palladium(II) acetate (2.3 mg, 10 μmol, 0.1 equiv), and 1,1′-bis(diphenylphosphino)ferrocene (11 mg, 20 μmol, 0.2 equiv) were combined in N,N-dimethylformamide (3 mL) and placed into a preheated oil bath at 90° C. for 30 minutes. The mixture was cooled to ambient temperature, poured into water (20 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were washed with water (50 mL) and brine (50 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexnaes:ethyl acetate containing 10% methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.70 (1H, br s), 7.77 (1H, d, J=8.2 Hz), 7.65 (1H, d, J=5.6 Hz), 7.54 (2H, d, J=8.3 Hz), 7.39 (2H, d, J=8.3 Hz), 7.27-7.24 (2H, in), 5.81 (2H, s), 4.78-4.70 (1H, m), 4.02 (1H, dd, J=10.8, 3.9 Hz), 3.97 (1H, br d, J=11.4 Hz), 3.80 (1H, ap t, J=10.5 Hz), 3.49 (1H, td, J=11.3, 3.1 Hz), 2.62 (3H, s), 2.22 (1H, ddd, J=17.2, 12.3, 5.0 Hz), 2.10 (1H, br d, J=11.3 Hz), 1.94-1.80 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 458.1642 [(M+H)+; calculated for C25H24N5O2S: 458.1645].

Workup

  1. extractionextracted with ethyl acetate (3×75 mL)
  2. washThe combined organic extracts were washed with water (50 mL) and brine (50 mL)
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexnaes:ethyl acetate containing 10% methanol)

Sources & evidence

ORD record
ord-910cf8cd1ff04f8893ae7d255ba44ffb
Source dataset
uspto-grants-2012_10
Patent number
US08293744B2

Reaction notes

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