1,2-Diaminocyclohexane, trans- → 3-[3-Fluoranyl-4-[5-Methoxy-4-Oxidanylidene-3-(2-Phenylpyrazol-3-Yl)pyridazin-1-Yl]phenyl]-1,3-Oxazolidin-2-One

HRID 1624799Notes

Reaction equation

HRID 1624799 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.[O:29]1[CH2:33][C:32](=O)[N:31]=[C-:30]1.N[C@@H]1CCCC[C@H]1N.[O-:43]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Cu]I.O>[F:1][C:2]1[CH:7]=[C:6]([N:31]2[CH2:32][CH2:33][O:29][C:30]2=[O:43])[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 532495662H-1,3-oxazol-2-id-4-oneHCID 594362141-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Product 1

HCID 468489173-[3-Fluoranyl-4-[5-Methoxy-4-Oxidanylidene-3-(2-Phenylpyrazol-3-Yl)pyridazin-1-Yl]phenyl]-1,3-Oxazolidin-2-OneYield 71.1%

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), 2-oxazolidone (52.2 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 1.5 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 washed with AcOEt and recrystallized from MeOH/H2O to give the title compound (159 mg, 71% yield) as a pale yellow solid: mp 218-220° C.; NMR (300 MHz, CDCl3): δ ppm 3.90 (3H, s), 4.03-4.08 (2H, m), 4.51-4.56 (2H, m), 6.42 (1H, t, J=9.0 Hz), 7.01 (1H, ddd, J=1.1, 2.3, 9.0 Hz), 7.30 (1H, d, J=1.9 Hz), 7.35-7.45 (5H, m), 7.66 (1H, dd, J=2.3, 13.6 Hz), 7.78 (21-1, d, J=1.9 Hz). LC-MS (ESI) m/z 448 [M+H]+. Anal. Calcd for C23H18FN5O4: C, 61.74; H, 4.06; N, 15.65. Found: C, 61.48; H, 4.07; N, 15.54.

Workup

  1. temperaturewas refluxed for 1.5 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. washThe residue was washed with AcOEt
  7. customrecrystallized from MeOH/H2O

Sources & evidence

ORD record
ord-89fd4b8c6ceb4891b2798f0ca8036a9c
Source dataset
uspto-grants-2014_07
Patent number
US08778944B2

Reaction notes

Loading…