Ethyl Acetate → 5-(5-Chlorobenzoxazol-6-yl)-2-pyridylamine

HRID 874605Notes

Reaction equation

HRID 874605 reaction equation
Br[C:2]1[C:10]([Cl:11])=[CH:9][C:5]2[N:6]=[CH:7][O:8][C:4]=2[CH:3]=1.[NH2:12][C:13]1[CH:18]=[CH:17][C:16](B2OC(C)(C)C(C)(C)O2)=[CH:15][N:14]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(=O)OCC>C(#N)C.O1CCOCC1.O>[Cl:11][C:10]1[C:2]([C:16]2[CH:17]=[CH:18][C:13]([NH2:12])=[N:14][CH:15]=2)=[CH:3][C:4]2[O:8][CH:7]=[N:6][C:5]=2[CH:9]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 584872776-Bromo-5-chlorobenzoxazole

Product 1

HCID 584869115-(5-Chlorobenzoxazol-6-yl)-2-pyridylamineYield 67.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 6-bromo-5-chlorobenzoxazole (30) (232 mg, 1 mmol), 2-aminopyridine-5-boronic acid pinacol ester (11) (220 mg, 1 mmol), Bis(di-tret-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium (II) (A-Phos) (70 mg, 0.1 mmol) and K3PO4 (212 mg, 1 mmol) in 2 ml ACN, 2 ml dioxane, 0.5 ml H2O was bubbled with argon before heated at 85° C. for 2 h. After cooling down to r.t., the reaction mixture was taken up in ethyl acetate, washed with aq. NaHCO3 and brine, dried over Na2SO4, concentrated to dryness. The resulting red solid was dissolved in DCM and subjected to silica gel column purification using 0-100% B (A: hexane; B: EA) to furnish 165.6 mg 31 as an orange solid (yield: 67.4%)

Workup

  1. customwas bubbled with argon
  2. temperatureAfter cooling down to r.t.
  3. washwashed with aq. NaHCO3 and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to dryness
  6. dissolutionThe resulting red solid was dissolved in DCM
  7. customsubjected to silica gel column purification

Sources & evidence

ORD record
ord-dab8db54af9744d3b373c3b1f57c0fbb
Source dataset
uspto-grants-2015_03
Patent number
US08980629B2

Reaction notes

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