Toluene → 6-[2-(2,4-Difluorophenyl)ethynyl]-3-nitro-pyridin-2-amine

HRID 2065782Notes

Reaction equation

HRID 2065782 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH2:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:19]([C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=1[F:28])#[CH:20].C1(C)C=CC=CC=1>C(#N)C.[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[F:28][C:22]1[CH:23]=[C:24]([F:27])[CH:25]=[CH:26][C:21]=1[C:19]#[C:20][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 8471TriethylamineHCID 27240356-Chloro-3-nitropyridin-2-ylamineHCID 50638201-Ethynyl-2,4-difluorobenzene

Product 1

HCID 677768706-[2-(2,4-Difluorophenyl)ethynyl]-3-nitro-pyridin-2-amineYield 92%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
2.5 °C

Procedure

6-Chloro-3-nitro-pyridin-2-ylamine (1254 g, 7.23 mol), triethylamine (1510 mL, 10.84 mol) and acetonitrile (10 L) are charged into a 20 L, 4-neck round bottom flask equipped with a mechanical stirrer under nitrogen. To the resulting yellow suspension, copper(I) iodide (13.9 g, 72.3 mmol) and bis(triphenylphosphine)palladium (II) chloride (50.72 g, 72.3 mmol) are added. The resulting pale orange suspension is cooled to 0-5° C. and then degassed during 10 min with nitrogen. A solution of 1-ethynyl-2,4-difluoro-benzene (1100 g, 7.95 mol) dissolved in acetonitrile (2.5 L) is added dropwise during 60 min. The resulting mixture is left stirring at RT (30° C.) overnight. The mixture is cooled to 0-5° C. Toluene (6 L) is added to the suspension and the mixture is stirred for 45 min and filtered though a frit. The solid is washed with toluene (3×3 L), water (2×3 L) and is dried overnight in a vacuum oven, to obtain the title compound as a yellow solid (1750 g, 92%). LC-ES/MS m/z 276 (M+1).

Workup

  1. customequipped with a mechanical stirrer under nitrogen
  2. customdegassed during 10 min with nitrogen
  3. additionis added dropwise during 60 min
  4. waitThe resulting mixture is left
  5. temperatureThe mixture is cooled to 0-5° C
  6. stirringthe mixture is stirred for 45 min
  7. filtrationfiltered though a frit
  8. washThe solid is washed with toluene (3×3 L), water (2×3 L)
  9. customis dried overnight in a vacuum oven

Sources & evidence

ORD record
ord-b601a9bcae84437ab18343b2ab0f900a
Source dataset
uspto-grants-2012_10
Patent number
US08288548B2

Reaction notes

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