Cesium carbonate → 3-Bromo-5-(6-tert-butyl-8-fluoro-1-oxo-1,2-dihydrophthalazin-2-yl)pyridine-4-carbaldehyde

HRID 407628Notes

Reaction equation

HRID 407628 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[NH:10][N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[Br:17][C:18]1[CH:19]=[N:20][CH:21]=[C:22](Br)[C:23]=1[CH:24]=[O:25].COC1C2C(=C3C(=CC=2)C(OC)=CC=N3)N=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>[Cu]I.O1CCOCC1>[Br:17][C:18]1[CH:19]=[N:20][CH:21]=[C:22]([N:10]2[N:9]=[CH:8][C:7]3[C:12](=[C:13]([F:15])[CH:14]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:6]=3)[C:11]2=[O:16])[C:23]=1[CH:24]=[O:25]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 27629983,5-Dibromo-4-pyridinecarboxaldehydeHCID 104622984,7-Dimethoxy-1,10-phenanthrolineHCID 594737656-(tert-Butyl)-8-fluorophthalazin-1(2H)-one

Product 1

HCID 866839253-Bromo-5-(6-tert-butyl-8-fluoro-1-oxo-1,2-dihydrophthalazin-2-yl)pyridine-4-carbaldehydeYield 29.3%

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 sealed tube equipped with a magnetic stirrer was charged with 6-tert-butyl-8-fluoro-1,2-dihydrophthalazin-1-one 101h (220 mg, 1.0 mmol), 3,5-dibromopyridine-4-carbaldehyde (530 mg, 2.0 mmol), CuI (190 mg, 1.0 mmol), 4,7-dimethoxy-1,10-phenanthroline (244 mg, 1.0 mmol), Cs2CO3 (652 mg, 2.0 mmol) and dioxane (8 mL). After three cycles of vacuum/argon flush, the mixture was heated at 110° C. for 5 h. It was then filtered and the filtrate was evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with ethyl acetate/petroleum ether (1:3, V/V) to afford 109a (118 mg, 29.3%) as a solid. LCMS: [M+H]+ 406

Workup

  1. customA sealed tube equipped with a magnetic stirrer
  2. customAfter three cycles of vacuum/argon flush
  3. filtrationIt was then filtered
  4. customthe filtrate was evaporated in vacuo
  5. customThe residue was purified by silica gel column chromatography
  6. washeluting with ethyl acetate/petroleum ether (1:3, V/V)

Sources & evidence

ORD record
ord-7f64fb5af8364cc8b54c3244a78fad26
Source dataset
uspto-grants-2014_06
Patent number
US08754077B2

Reaction notes

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