Imidazole → HCID 58072364, compound

HRID 2089990Notes

Reaction equation

HRID 2089990 reaction equation
[F:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[N:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]2[N:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:21]=[CH:20][CH:19]=2)=[N:10]1.[NH:29]1[CH:33]=[CH:32][N:31]=[CH:30]1.N[C@@H]1CCCC[C@H]1N.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.[Cu]I.O>[F:1][C:2]1[CH:7]=[C:6]([N:29]2[CH:33]=[CH:32][N:31]=[CH:30]2)[CH:5]=[CH:4][C:3]=1[N:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]2[N:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:21]=[CH:20][CH:19]=2)=[N:10]1

Participants

8

Reactant 4

HCID 795ImidazoleHCID 10796Cesium carbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 594362141-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Product 1

HCID 58072364HCID 58072364, compoundYield 8%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A suspension of 1-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (244 mg, 0.5 mmol), imidazole (40.8 mg, 0.6 mmol), CuI (9.5 mg, 0.05 mmol), trans-1,2-diaminocyclohexane (0.012 mL, 0.1 mmol), and Cs2CO3. (326 mg, 1.0 mmol) in 1,4-dioxane (2 mL) was refluxed for 4 h under Ar atmosphere. The reaction mixture was poured into water and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography eluting with AcOEt/THF (1/0-0/1) and crystallized from MeOH to give the title compound (16.5 mg, 8% yield) as a white solid: mp 235-236° C. (dec); 1H NMR (300 MHz, CDCl3): δ ppm 3.93 (3H, s), 6.49 (1H, t, J=8.7 Hz), 7.03 (1H, ddd, J=1.1, 2.3, 8.7 Hz), 7.22-7.27 (3H, m), 7.35 (1H, d, J=1.9 Hz), 7.38-7.49 (5H, m), 7.80 (1H, d, J=1.9 Hz), 7.82 (1H, d, J=2.6 Hz), 7.86 (1H, t, J=1.1 Hz). LC-MS (ESI) m/z 429 [M+H]+. Anal. Calcd for C23H17FN6O2: C, 64.48; H, 4.00; N, 19.62. Found: C, 64.35 H, 3.90; N, 19.43.

Workup

  1. extractionextracted with AcOEt
  2. washThe extract was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by basic silica gel column chromatography
  6. washeluting with AcOEt/THF (1/0-0/1)
  7. customcrystallized from MeOH

Sources & evidence

ORD record
ord-7065778abfe7435ea93ead4ee8b9541d
Source dataset
uspto-grants-2013_05
Patent number
US08435995B2

Reaction notes

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