Ethyl Acetate → 5-(3,5-Dimethylbenz[d]isoxazol-6-yl)pyrazine-2-ylamine

HRID 2272200Notes

Reaction equation

HRID 2272200 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]=[N: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[N: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 179989875-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-amineHCID 584870706-Bromo-3,5-dimethylbenzo[d]isoxazole

Product 1

HCID 584866795-(3,5-Dimethylbenz[d]isoxazol-6-yl)pyrazine-2-ylamineYield 26.1%

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) (54 mg, 0.24 mmol), 2-aminopyrazine-5-boronic acid pinacol ester (14) (79 mg, 0.358 mmol), bis(ditertbutyl(4-dimethylaminophenyl)phosphine)dichloropalladium (II) (25 mg, 10% mol) and K3PO4 (76 mg) in 1 ml ACN, 1 ml dioxane, 0.5 ml H2O was bubbled with argon before heated at 85° C. for 3 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-dimethylbenz[d]isoxazol-6-yl)pyrazine-2-ylamine (109) (15 mg, yield: 26.1%, purity>95%) as light 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-25577e589412407199aeb62c767dacd7
Source dataset
uspto-grants-2015_09
Patent number
US09120751B2

Reaction notes

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