Sodium Carbonate → 4-(2-(4-Aminophenoxy)pyridin-3-yl)-5-methylisoxazol-3-amine

HRID 227775

Reaction equation

HRID 227775 reaction equation
[NH2:1][C:2]1[C:6](Br)=[C:5]([CH3:8])[O:4][N:3]=1.CC1(C)C(C)(C)OB([C:17]2[C:18]([O:23][C:24]3[CH:29]=[CH:28][C:27]([NH2:30])=[CH:26][CH:25]=3)=[N:19][CH:20]=[CH:21][CH:22]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[NH2:30][C:27]1[CH:28]=[CH:29][C:24]([O:23][C:18]2[C:17]([C:6]3[C:2]([NH2:1])=[N:3][O:4][C:5]=3[CH3:8])=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:25][CH:26]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 27744644-Bromo-5-methyl-1,2-oxazol-3-amineHCID 574164444-(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yloxy)benzenamine

Product 1

HCID 577562454-(2-(4-Aminophenoxy)pyridin-3-yl)-5-methylisoxazol-3-amine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a 20 mL sealed tube was added dioxane (1.0 mL), which was purged with nitrogen for 5 minutes and the tube sealed. To this was added 3-amino-4-bromo-5-methylisoxazole (0.100 g, 0.565 mmol), 4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yloxy)benzenamine (0.265 g, 0.847 mmol), 2.0M aqueous sodium carbonate (0.565 mL, 1.13 mmol) and the tube was purged with nitrogen and sealed. To the mixture was added tri-t-butylphosphonium tetrafluoroborate (0.037 g, 0.13 mmol), tris(dibenzylideneacetone)dipalladium (0)(0.039 g, 0.042 mmol) and the tube was purged with nitrogen, sealed and heated to 100° C. with stirring for 5 hours. The mixture was cooled to RT, passed through pad of silica, which was washed with 100% CH2Cl2:MeOH:NH4OH (90:10: 1)/CH2Cl2. The eluent was concentrated and purified on a Gilson reverse phase chromatography system. The product fractions were extracted into CH2Cl2, washed 1× saturated NaHCO3, 1×H2O, dried with Na2SO4, filtered through fritted funnel and concentrated to yield 4-(2-(4-aminophenoxy)pyridin-3-yl)-5-methylisoxazol-3-amine as light yellow solid. MS m/z=283 [M+1]+. Calc'd for C15H14N4O2: 282.30.

Workup

  1. customIn a 20 mL sealed tube
  2. customwas purged with nitrogen for 5 minutes
  3. customthe tube sealed
  4. customthe tube was purged with nitrogen
  5. customsealed
  6. customthe tube was purged with nitrogen
  7. customsealed
  8. temperatureThe mixture was cooled to RT
  9. washwas washed with 100% CH2Cl2:MeOH:NH4OH (90:10: 1)/CH2Cl2
  10. concentrationThe eluent was concentrated
  11. custompurified on a Gilson reverse phase chromatography system
  12. extractionThe product fractions were extracted into CH2Cl2
  13. washwashed 1× saturated NaHCO3, 1×H2O
  14. dry with materialdried with Na2SO4
  15. filtrationfiltered through fritted funnel
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-5441c20780344f7d866157fb221fffe2
Source dataset
uspto-grants-2009_07
Patent number
US07560551B2

Linked notes

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