Water → 5-[(5-Methyl-3-phenyl-isoxazol-4-ylmethyl)-amino]-pyrazine-2-carboxylic acid isopropylamide

HRID 600483Notes

Reaction equation

HRID 600483 reaction equation
[CH:1]([NH2:4])([CH3:3])[CH3:2].C[Al](C)C.C[O:10][C:11]([C:13]1[CH:18]=[N:17][C:16]([NH:19][CH2:20][C:21]2[C:22]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[N:23][O:24][C:25]=2[CH3:26])=[CH:15][N:14]=1)=O.O>O1CCOCC1>[CH:1]([NH:4][C:11]([C:13]1[CH:18]=[N:17][C:16]([NH:19][CH2:20][C:21]2[C:22]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[N:23][O:24][C:25]=2[CH3:26])=[CH:15][N:14]=1)=[O:10])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 6363IsopropylamineHCID 16682925TrimethylaluminumHCID 684456305-[(5-Methyl-3-phenyl-isoxazol-4-ylmethyl)-amino]-pyrazine-2-carboxylic acid methyl ester

Product 1

HCID 426358785-[(5-Methyl-3-phenyl-isoxazol-4-ylmethyl)-amino]-pyrazine-2-carboxylic acid isopropylamideYield 85.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of isopropylamine (0.69 mL, 8 mmol) in dioxane (5 mL) was added dropwise trimethylaluminum solution (2M solution in hexane, 4 mL, 8 mmol). After stirring for 1 h at room temperature a suspension of 5-[(5-methyl-3-phenyl-isoxazol-4-ylmethyl)-amino]-pyrazine-2-carboxylic acid methyl ester (650 mg, 2 mmol) in dioxane (5 mL) was added. The reaction mixture was stirred at 90° C. for 90 min, cooled to room temperature and poured into water. Extraction with ethyl acetate and washing with saturated aqueous Seignette salt solution was followed by drying of the organic phase over sodium sulfate and evaporation which afforded an oil. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 20:80) afforded the title compound (600 mg, 85%) as a white solid MS: m/e=352.3 [M+H]+.

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred at 90° C. for 90 min
  3. temperaturecooled to room temperature
  4. extractionExtraction with ethyl acetate
  5. washwashing with saturated aqueous Seignette salt solution
  6. dry with materialby drying of the organic phase over sodium sulfate and evaporation which
  7. customafforded an oil
  8. customPurification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 20:80)

Sources & evidence

ORD record
ord-e3699bbf3d88467abc4a0835a2550311
Source dataset
uspto-grants-2011_03
Patent number
US07902201B2

Reaction notes

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