3-Amino-5-methylisoxazole → 5-Bromo-1-methyl-3-(5-methylisoxazol-3-ylamino)pyridin-2(1H)-one

HRID 2069846Notes

Reaction equation

HRID 2069846 reaction equation
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6]([Br:8])[CH:7]=1.[CH3:11][C:12]1[O:16][N:15]=[C:14]([NH2:17])[CH:13]=1.[O-]C1C=CC=CC=1.[Na+]>O1CCOCC1.C(OC(=O)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].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Br:8][C:6]1[CH:7]=[C:2]([NH:17][C:14]2[CH:13]=[C:12]([CH3:11])[O:16][N:15]=2)[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=1

Participants

8

Reactant 3

HCID 661723-Amino-5-methylisoxazoleHCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-oneHCID 4445035Phenolate Sodium

Product 1

HCID 592164565-Bromo-1-methyl-3-(5-methylisoxazol-3-ylamino)pyridin-2(1H)-oneYield 47%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 3,5-dibromo-1-methyl-1H-pyridin-2-one (200 mg, 0.75 mmol) in 4 ml dioxane was placed in a microwave tube filled with argon. To this solution was added Xantphos (13 mg, 0.022 mmol), Pd2dba3 (16.8 mg, 18.3 mmol), 5-methyl-isoxazole-3-ylamine (73.6 mg, 0.75 mmol) and sodium phenoxide (127.6 mg, 1.1 mmol).The tube was sealed and heated at 150° ° C. using microwave irradiation. After cooling the reaction mixture was diluted with ethylacetate, washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was triturated with ethylacetate. The resulting mixture was filtered affording 100 mg (47% yield) of 5-Bromo-1-methyl-3-(5-methyl-isoxazol-3-ylamino)-1H-pyridin-2-one which was used in the next step without additional purification.

Workup

  1. additionfilled with argon
  2. customwas sealed
  3. temperatureheated at 150° ° C
  4. custommicrowave irradiation
  5. temperatureAfter cooling the reaction mixture
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was triturated with ethylacetate
  10. filtrationThe resulting mixture was filtered

Sources & evidence

ORD record
ord-415e1354a3d641b4a7d468c631f09250
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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