Potassium Carbonate → 4-Amino-6-(4-methoxy-3-trifluoromethyl-phenyl)-3-nitro-pyridine-2-carbonitrile

HRID 2246437Notes

Reaction equation

HRID 2246437 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([C:9]#[N:10])[C:3]=1[N+:11]([O-:13])=[O:12].[CH3:14][O:15][C:16]1[CH:21]=[CH:20][C:19](B(O)O)=[CH:18][C:17]=1[C:25]([F:28])([F:27])[F:26].C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1COCC1>[NH2:1][C:2]1[CH:7]=[C:6]([C:19]2[CH:20]=[CH:21][C:16]([O:15][CH3:14])=[C:17]([C:25]([F:26])([F:28])[F:27])[CH:18]=2)[N:5]=[C:4]([C:9]#[N:10])[C:3]=1[N+:11]([O-:13])=[O:12]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 177500524-Methoxy-3-(trifluoromethyl)benzeneboronic acidHCID 552704134-Amino-6-chloro-3-nitro-pyridine-2-carbonitrile

Product 1

HCID 589381164-Amino-6-(4-methoxy-3-trifluoromethyl-phenyl)-3-nitro-pyridine-2-carbonitrileYield 26.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

A stirred mixture 4-amino-6-chloro-3-nitro-pyridine-2-carbonitrile (152 mg, 0.76 mmol), 4-methoxy-3-trifluoromethylphenylboronic acid (332 mg,1.51 mmol), tetrakis(triphenylphosphine)palladium(0) (115 mg, 10 mol %), potassium carbonate (418 mg, 3.03 mmol) and THF (5 ml) was degassed under a stream of nitrogen before heating in the Smith Creator microwave at 150° C. for 10 minutes. The crude mixture was concentrated under reduced pressure to remove THF before partitioning between ethyl acetate (20 ml) and water (20 ml). The organic layer was separated, dried over sodium sulfate and concentrated under reduced pressure to give a dark brown oil. Mixture was flash chromatographed over silica (10 g Combiflash cartridge, 7:3 heptane/ethyl acetate to 1:1 heptane/ethyl acetate) to afford 68 mg of 4-amino-6-(4-methoxy-3-trifluoromethyl-phenyl)-3-nitro-pyridine-2-carbonitrile as an orange solid. 1H NMR (DMSO) δ 8.25 (d, 1H), 8.18 (m, 2H), 7.62 (s, 2H), 7.46 (d, 1H), 3.99 (s, 3H). MS m/z 339.3 (M+1).

Workup

  1. concentrationThe crude mixture was concentrated under reduced pressure
  2. customto remove THF
  3. custombefore partitioning between ethyl acetate (20 ml) and water (20 ml)
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customto give a dark brown oil
  8. customchromatographed over silica (10 g Combiflash cartridge, 7:3 heptane/ethyl acetate to 1:1 heptane/ethyl acetate)

Sources & evidence

ORD record
ord-e5fbb66c4ebb4c69bd26dff723c5a6c3
Source dataset
uspto-grants-2010_03
Patent number
US07687515B2

Reaction notes

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