Diisopropylethylamine → 2-Chloro-5-((5-fluoro-4-methylpyridin-3-yl)ethynyl)isonicotinaldehyde

HRID 468952Notes

Reaction equation

HRID 468952 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][CH:6]=[C:7]([F:10])[C:8]=1[CH3:9])#[CH:2].Br[C:12]1[C:13]([CH:19]=[O:20])=[CH:14][C:15]([Cl:18])=[N:16][CH:17]=1.C(N(CC)C(C)C)(C)C>O1CCOCC1.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:18][C:15]1[CH:14]=[C:13]([C:12]([C:2]#[C:1][C:3]2[CH:4]=[N:5][CH:6]=[C:7]([F:10])[C:8]=2[CH3:9])=[CH:17][N:16]=1)[CH:19]=[O:20]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 534183815-Bromo-2-chloropyridine-4-carbaldehydeHCID 866749813-Ethynyl-5-fluoro-4-methylpyridine

Product 1

HCID 866749822-Chloro-5-((5-fluoro-4-methylpyridin-3-yl)ethynyl)isonicotinaldehydeYield 78%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 3-ethynyl-5-fluoro-4-methyl-pyridine (240 mg, 1.78 mmol), 5-bromo-2-chloro-pyridine-4-carbaldehyde (392 mg, 1.78 mmol), N,N-diisopropylethylamine (0.62 mL, 3.55 mmol), dichlorobis(triphenylphosphine)palladium(II) (64 mg, 0.089 mmol), and cuprous iodide (17 mg, 0.089 mmol) in dioxane (5 mL) was heated at 60° C. for 1 hour. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered and concentrated in vacuo to provide a residue that was purified by flash chromatography (12 g, Silica, 0-70% ethyl acetate in heptane). Desired fractions were combined and evaporated in vacuo to afford the title compound as a pale yellow solid (380 mg, 78%), which was used in the next step without further purification.

Workup

  1. washwashed with water (50 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto provide a residue that
  7. customwas purified by flash chromatography (12 g, Silica, 0-70% ethyl acetate in heptane)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-18dc961d6851477c8b8f7f38d7a9d39a
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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