Water → HCID 66633644, compound

HRID 2166971Notes

Reaction equation

HRID 2166971 reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:8]2[S:9][CH:10]=[CH:11][N:12]=2)[CH:7]=1.Br[C:14]1[N:19]=[C:18]([C:20]#[N:21])[CH:17]=[CH:16][CH:15]=1.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.O>CN(C=O)C.[Pd](Cl)Cl.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([C:8]2[S:9][C:10]([C:14]3[N:19]=[C:18]([C:20]#[N:21])[CH:17]=[CH:16][CH:15]=3)=[CH:11][N:12]=2)[CH:5]=[N:4][CH:3]=1

Participants

8

Reactant 4

HCID 962WaterHCID 80271Tri-o-tolylphosphineHCID 151008596-Bromopyridine-2-carbonitrileHCID 66633860HCID 66633860, compound

Product 1

HCID 66633644HCID 66633644, compoundYield 61%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

Under argon, 3-fluoro-5-(1,3-thiazol-2-yl)pyridine (0.99 g, 5.47 mmol) and 6-bromopyridin-2-carbonitrile (1.0 g, 5.47 mmol) were initially charged in DMF (15 ml). After 10 min, at room temperature, tris(2-methylphenyl)phosphine (0.13 g, 0.23 mmol) and palladium(II) chloride (0.1 g, 0.55 mmol) were added. The reaction mixture was stirred at 130° C. for 14 h. After cooling, water and ethyl acetate were added and the precipitated product was filtered off with suction. The organic phase of the filtrate was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulphate and the solvent was removed under reduced pressure. The residue was stirred with dichloromethane and filtered off with suction. This gave a total of 0.94 g (61% of theory) of 6-[2-(5-fluoropyridin-3-yl)-1,3-thiazol-5-yl]pyridine-2-carbonitrile.

Workup

  1. temperatureAfter cooling
  2. filtrationthe precipitated product was filtered off with suction
  3. customThe organic phase of the filtrate was removed
  4. extractionthe aqueous phase was extracted three times with ethyl acetate
  5. dry with materialThe combined organic phases were dried over magnesium sulphate
  6. customthe solvent was removed under reduced pressure
  7. stirringThe residue was stirred with dichloromethane
  8. filtrationfiltered off with suction

Sources & evidence

ORD record
ord-b32271fffe754067b717d47f4d20b5d7
Source dataset
uspto-grants-2015_06
Patent number
US09044015B2

Reaction notes

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