Cesium carbonate → N-(4-(3,4'-bipyridin-2-yloxy)phenyl)benzo[d]thiazol-2-amine

HRID 410191

Reaction equation

HRID 410191 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[C:8]([O:13][C:14]3[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=3)=[N:9][CH:10]=[CH:11][CH:12]=2)=[CH:3][CH:2]=1.Br[C:22]1[S:23][C:24]2[CH:30]=[CH:29][CH:28]=[CH:27][C:25]=2[N:26]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC(O)(C)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:9]1[CH:10]=[CH:11][CH:12]=[C:7]([C:4]2[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=2)[C:8]=1[O:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:22]2[S:23][C:24]3[CH:30]=[CH:29][CH:28]=[CH:27][C:25]=3[N:26]=2)=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6120402-Bromo-1,3-benzothiazoleHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 593271694-(3-(Pyridin-4-yl)pyridin-2-yloxy)benzenamine

Product 1

HCID 59326934N-(4-(3,4'-bipyridin-2-yloxy)phenyl)benzo[d]thiazol-2-amine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 22595558Toluene tert-butyl alcoholSolvent

Procedure

A 25 ml round bottomed flask was charged with 4-(3-(pyridin-4-yl)pyridin-2-yloxy)benzenamine (0.1531 g, 0.58 mmol), 2-bromobenzo[d]thiazole (0.1874 g, 0.88 mmol), Palladium acetate (0.0264 g, 0.12 mmol), 2-(dicyclohexylphosphino)biphenyl (0.0878 g, 0.23 mmol), and cesium carbonate (0.077 ml, 0.81 mmol) in toluene/t-BuOH (5/1) at 100° C. overnight. Upon completion, the reaction was allowed to cool to room temperature. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column (25M), eluting with a gradient of 1% to 5% MeOH in DCM. Further purification was performed by reverse-phase preparative HPLC using a Phenomenex Gemini column, 5 micron, 150×30 mm, 0.1% TFA in ACN/H2O, gradient 10% to 100% over 15 min. The product peak fractions were collected and organic solvents were removed. The aqueous solution was diluted with water (5 mL) and sodium bicarbonate was added until the pH˜10. The solution was extracted with DCM. The organic extract was washed with water, brine, dried with magnesium sulfate, filtered, and concentrated to provide N-(4-(3,4′-bipyridin-2-yloxy)phenyl)benzo[d]thiazol-2-amine. MS (ESI, pos. ion) m/z: 397.0 (M+1). IC50 (uM) +++++.

Workup

  1. customchromatographed through a Biotage pre-packed silica gel column (25M)
  2. washeluting with a gradient of 1% to 5% MeOH in DCM
  3. customFurther purification
  4. customover 15 min
  5. customThe product peak fractions were collected
  6. customorganic solvents were removed
  7. additionThe aqueous solution was diluted with water (5 mL) and sodium bicarbonate
  8. additionwas added until the pH˜10
  9. extractionThe solution was extracted with DCM
  10. extractionThe organic extract
  11. washwas washed with water, brine
  12. dry with materialdried with magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-2e792bb8868947dcacb7f327cb438c67
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Linked notes

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