Cesium fluoride → HCID 57898949, compound

HRID 911022Notes

Reaction equation

HRID 911022 reaction equation
Br[C:2]1[C:3]([S:15][C:16]2[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:23])=[CH:4][C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)=[N:6][CH:7]=1.CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)[O:26]1.C1(P(C2CCCC2)C2CCCC2)CCCC1.[F-].[Cs+]>C(#N)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:23][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([Cl:22])[C:16]=1[S:15][C:3]1[CH:4]=[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)[N:6]=[CH:7][C:2]=1[OH:26]

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 2733548Bis(pinacolato)diboraneHCID 4463278Phosphine, tricyclopentyl-HCID 86634751N-(5-bromo-4-(2,6-dichlorophenylthio)pyridin-2-yl)-4-methylthiazol-2-amine

Product 1

HCID 57898949HCID 57898949, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A degassed mixture of N-(5-bromo-4-(2,6-dichlorophenylthio)pyridin-2-yl)-4-methylthiazol-2-amine (1.18 g, 2.66 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (1.35 g, 5.32 mmol), Pd(OAc)2 (60 mg, 0.27 mmol), tricyclopentylphosphine (93 mg. 0.40 mmol) and cesium fluoride (3.64 g, 23.9 mmol) in acetonitrile is heated at 90° C. for 5 hours. The reaction mixture is cooled and partitioned between ether and water. The crude product is dissolved in THF. N-morpholine N-oxide (1.40 g, 12.0 mmol) is added and the reaction mixture is heated at reflux for 12 hours. The reaction mixture is cooled and partitioned between ether and water. The organic layer is washed with water and brine, dried and concentrated. The residue is purified by silica gel chromatography, eluting with 10-20% EtOAc in hexanes to afford 4-(2,6-dichlorophenylthio)-6-(4-methylthiazol-2-ylamino)pyridin-3-ol.

Workup

  1. temperatureThe reaction mixture is cooled
  2. custompartitioned between ether and water
  3. dissolutionThe crude product is dissolved in THF
  4. temperaturethe reaction mixture is heated
  5. temperatureat reflux for 12 hours
  6. temperatureThe reaction mixture is cooled
  7. custompartitioned between ether and water
  8. washThe organic layer is washed with water and brine
  9. customdried
  10. concentrationconcentrated
  11. customThe residue is purified by silica gel chromatography
  12. washeluting with 10-20% EtOAc in hexanes

Sources & evidence

ORD record
ord-5e61f955ea3441db8f3449cea111b708
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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