1,2-Diaminocyclohexane, trans- → HCID 58072227, compound

HRID 1407320Notes

Reaction equation

HRID 1407320 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[CH2:34][CH2:33][O:32][CH2:31][C:30]1=[O:35].N[C@@H]1CCCC[C@H]1N.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Cu]I.O>[F:1][C:2]1[CH:7]=[C:6]([N:29]2[CH2:34][CH2:33][O:32][CH2:31][C:30]2=[O:35])[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 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 669533-MorpholinoneHCID 594362141-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Product 1

HCID 58072227HCID 58072227, compoundYield 59%

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), 3-morpholinone (60.7 mg, 0.6 mmol), CuI (9.5 mg, 0.05 mmol), trans-1,2-diaminocyclohexane (0.012 mL, 0.1 mmol), and K3PO4 (212 mg, 1.0 mmol) in 1,4-dioxane (2 mL) was refluxed for 6 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 and recrystallized from MeOH/H2O to give the title compound (136 mg, 59% yield) as a white solid: mp 193-195° C.; 1H NMR (300 MHz, CDCl3): δ ppm 3.75-3.79 (2H, m), 3.90 (3H, s), 4.04-4.07 (2H, m), 4.35 (2H, s), 6.41 (1H, t, J=9.0 Hz), 7.00 (1H, ddd, J=1.1, 2.3, 9.0 Hz), 7.31 (1H, d, J=2.3 Hz), 7.33-7.46 (6H, m), 7.78-7.80 (2H, m). LC-MS (ESI) m/z 462 [M+H]+. Anal. Calcd for C24H20FN5O4: C, 62.47; H, 4.37; N, 15.18. Found: C, 62.31; H, 4.33; N, 15.25.

Workup

  1. temperaturewas refluxed for 6 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
  8. customrecrystallized from MeOH/H2O

Sources & evidence

ORD record
ord-de068badeecc4118b3b570418a290ad7
Source dataset
uspto-grants-2014_12
Patent number
US08916566B2

Reaction notes

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