Imidazole → HCID 58072364, compound

HRID 1805686Notes

Reaction equation

HRID 1805686 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, 64.35H, 3.90; N, 19.43.

Workup

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

Sources & evidence

ORD record
ord-4cf45c0b37e34e46aa237aed3b4709fe
Source dataset
uspto-grants-2013_01
Patent number
US08354411B2

Reaction notes

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