Ethyl Acetate → 5-(3,5-Dimethylbenzo[d]isoxazol-6-yl)-2-pyridylamine

HRID 874627Notes

Reaction equation

HRID 874627 reaction equation
Br[C:2]1[C:11]([CH3:12])=[CH:10][C:5]2[C:6]([CH3:9])=[N:7][O:8][C:4]=2[CH:3]=1.[NH2:13][C:14]1[CH:19]=[CH:18][C:17](B2OC(C)(C)C(C)(C)O2)=[CH:16][N:15]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(=O)OCC>C(#N)C.O1CCOCC1.O>[CH3:9][C:6]1[C:5]2[CH:10]=[C:11]([CH3:12])[C:2]([C:17]3[CH:18]=[CH:19][C:14]([NH2:13])=[N:15][CH:16]=3)=[CH:3][C:4]=2[O:8][N:7]=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 584870706-Bromo-3,5-dimethylbenzo[d]isoxazole

Product 1

HCID 584869675-(3,5-Dimethylbenzo[d]isoxazol-6-yl)-2-pyridylamineYield 91.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 6-bromo-3,5-dimethylbenz[d]isoxazole (104) (46 mg, 0.2 mmol), 2-aminopyridine-5-boronic acid pinacol ester (11) (66 mg, 0.3 mmol), bis(ditertbutyl(4-dimethylaminophenyl)phosphine)dichloropalladium (II) (21 mg, 10% mol) and K3PO4 (64 mg, 0.3 mmol) in 0.5 ml ACN, 0.5 ml dioxane, 0.25 ml H2O was bubbled with argon before heated at 85° C. for 2.5 h. After cooling down to r.t., the reaction mixture was taken up in EA, washed with aq. NaHCO3 and brine. Org. phase was dried over Na2SO4, concentrated and then subjected to silica gel flash column chromatography (0-100% B, A: hexane; B: EA) to give 5-(3,5-dimethylbenzo[d]isoxazol-6-yl)-2-pyridylamine (105) (44 mg, yield: 91.9%, purity>90%) as yellow solid.

Workup

  1. customwas bubbled with argon
  2. temperatureAfter cooling down to r.t.
  3. washwashed with aq. NaHCO3 and brine
  4. dry with materialphase was dried over Na2SO4
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-a58b3515a08d45b88a2f0249172f12eb
Source dataset
uspto-grants-2015_03
Patent number
US08980629B2

Reaction notes

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