1,2-Diaminocyclohexane, trans- → 1-[4-(5,5-Dimethyl-2-oxo-1,3-oxazolidin-3-yl)-2-fluorophenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1624848Notes

Reaction equation

HRID 1624848 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.[CH3:29][C:30]1([CH3:36])[O:34][C:33](=[O:35])[NH:32][CH2:31]1.N[C@@H]1CCCC[C@H]1N.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C([O-])(O)=O.[Na+]>O1CCOCC1.[Cu]I>[CH3:29][C:30]1([CH3:36])[O:34][C:33](=[O:35])[N:32]([C:6]2[CH:5]=[CH:4][C:3]([N:9]3[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]4[N:22]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[N:21]=[CH:20][CH:19]=4)=[N:10]3)=[C:2]([F:1])[CH:7]=2)[CH2:31]1

Participants

8

Reactant 5

HCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 1368922-Oxazolidinone, 5,5-dimethyl-HCID 516892Sodium BicarbonateHCID 594362141-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Product 1

HCID 468490801-[4-(5,5-Dimethyl-2-oxo-1,3-oxazolidin-3-yl)-2-fluorophenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 66.2%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A suspension of 1-(2-fluoro-4-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (244 mg, 0.500 mmol), 5,5-dimethyl-1,3-oxazolidin-2-one (69.1 mg, 0.600 mmol), trans-1,2-diaminocyclohexane (0.012 mL, 0.100 mmol), CuI (9.5 mg, 0.050 mmol), and K3PO4 (212 mg, 1.00 mmol) in 1,4-dioxane (2.0 mL) was stirred at 110° C. under Ar atmosphere. The reaction mixture was poured into 5% NaHCO3 aqueous solution (20 mL) and extracted with AcOEt (20 mL×3). The combined organic phase was washed with brine (40 mL), dried with MgSO4, and evaporated. The residue was purified by basic silica gel column chromatography (MeOH/AcOEt=0%-10%) to give the title compound (157.4 mg, 66% yield): 1H NMR (300 MHz, DMSO-d6): δ ppm 1.49 (6H, s), 3.78 (3H, s), 3.89 (2H, s), 6.97 (1H, d, J=1.9 Hz), 7.05 (1H, t, J=9.0 Hz), 7.31 (1H, d, J=8.7 Hz), 7.31 (1H, t, J=1.7 Hz), 7.33 (1H, s), 7.37-7.48 (3H, m), 7.68 (1H, dd, J=13.4, 2.5 Hz), 7.79 (1H, d, J=1.9 Hz), 8.46 (1H, d, J=2.3 Hz). LC-MS (ESI) m/z 476 [M+H]+. Anal. Calcd for C25H22FN5O4: C, 63.15; H, 4.66; N, 14.73. Found: C, 63.09; H, 4.70; N, 14.85.

Workup

  1. extractionextracted with AcOEt (20 mL×3)
  2. washThe combined organic phase was washed with brine (40 mL)
  3. dry with materialdried with MgSO4
  4. customevaporated
  5. customThe residue was purified by basic silica gel column chromatography (MeOH/AcOEt=0%-10%)

Sources & evidence

ORD record
ord-7c296ef40cd34409a40bd3a12d018a76
Source dataset
uspto-grants-2014_07
Patent number
US08778944B2

Reaction notes

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