Toluene → HCID 66995430, compound

HRID 562922Notes

Reaction equation

HRID 562922 reaction equation
C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1.[C:14]([C:16]1[CH:17]=[C:18]([C:30]2[CH:31]=[C:32]([CH:37]=[CH:38][N:39]=2)[C:33]([O:35][CH3:36])=[O:34])[CH:19]=[CH:20][C:21]=1OS(C(F)(F)F)(=O)=O)#[N:15].[CH:40]([Si:43]([CH:55]([CH3:57])[CH3:56])([CH:52]([CH3:54])[CH3:53])[N:44]1[CH:48]=[CH:47][C:46](B(O)O)=[CH:45]1)([CH3:42])[CH3:41]>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.O>[C:14]([C:16]1[CH:17]=[C:18]([C:30]2[CH:31]=[C:32]([CH:37]=[CH:38][N:39]=2)[C:33]([O:35][CH3:36])=[O:34])[CH:19]=[CH:20][C:21]=1[C:46]1[CH:47]=[CH:48][N:44]([Si:43]([CH:52]([CH3:54])[CH3:53])([CH:55]([CH3:57])[CH3:56])[CH:40]([CH3:41])[CH3:42])[CH:45]=1)#[N:15]

Participants

7

Reactant 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 27633031-(Triisopropylsilyl)pyrrole-3-boronic acidHCID 86616562HCID 86616562, compound

Product 1

HCID 66995430HCID 66995430, compoundYield 5.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
130 °C

Procedure

58 mg of tetrakis(triphenylphosphine)palladium and 208 mg of potassium carbonate were added to a toluene (10 ml) solution of 386 mg of methyl 2-(3-cyano-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)isonicotinate and 534 mg of 1-(triisopropylsilyl)pyrrole-3-boronic acid, then this was irradiated with microwaves and heated at 130° C. in a nitrogen atmosphere for 1 hour. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5 to 70:30) to obtain 24 mg of methyl 2-{3-cyano-4-[1-(triisopropylsilyl)-1H-pyrrol-3-yl]phenyl}isonicotinate. (2) 24 mg of this compound was dissolved in 1 ml of THF, and 63 μL of 1 M tetrabutylammonium fluoride/THF solution was added thereto, followed by stirring at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=90:10 to 70:30) to obtain 6 mg of methyl 2-[3-cyano-4-(1H-pyrrol-3-yl)phenyl]isonicotinate. (3) 6 mg of this compound was dissolved in a mixture of 0.5 ml of methanol and 0.5 ml of THF, and 22 μl of aqueous 1 M sodium hydroxide solution was added, followed by heating at 60° C. for 2 hours. The reaction liquid was cooled, and the solvent was removed under reduced pressure. Water was added to the residue, followed by neutralization with 1 M hydrochloric acid. The precipitated crystal was collected by filtration and washed with a mixture of ethanol and water to obtain 1.5 mg of 2-[3-cyano-4-(1H-pyrrol-3-yl)phenyl]isonicotinic acid.

Workup

  1. customthis was irradiated with microwaves
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with brine
  4. customdried
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5 to 70:30)

Sources & evidence

ORD record
ord-42e6bc868a224bd19b8bd3f0f68e6ffa
Source dataset
uspto-grants-2011_11
Patent number
US08067446B2

Reaction notes

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