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

HRID 2245742Notes

Reaction equation

HRID 2245742 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

Conditions

Temperature
150 °C

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), Pd2 dba3 (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. customThe tube was sealed
  3. custommicrowave irradiation
  4. temperatureAfter cooling the reaction mixture
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was triturated with ethylacetate
  9. filtrationThe resulting mixture was filtered

Sources & evidence

ORD record
ord-b512ea3ef722485db189c1a33a9c1868
Source dataset
uspto-grants-2010_03
Patent number
US07683064B2

Reaction notes

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