Sulfuric acid magnesium salt (1:1) → HCID 24783156, compound

HRID 1984666Notes

Reaction equation

HRID 1984666 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH3:7])[N:6]=1.C[Al](C)C.C[O:13][C:14](=O)[C:15]1[CH:20]=[CH:19][N:18]=[C:17]([C:21]#[C:22][C:23]2[C:24]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[N:25][O:26][C:27]=2[CH3:28])[CH:16]=1.S([O-])([O-])(=O)=O.[Mg+2]>O1CCOCC1.O>[CH3:28][C:27]1[O:26][N:25]=[C:24]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]=1[C:22]#[C:21][C:17]1[CH:16]=[C:15]([CH:20]=[CH:19][N:18]=1)[C:14]([NH:1][C:2]1[S:3][CH:4]=[C:5]([CH3:7])[N:6]=1)=[O:13]

Participants

7

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 741432-Amino-4-methylthiazoleHCID 16682925TrimethylaluminumHCID 24783153HCID 24783153, compound

Product 1

HCID 24783156HCID 24783156, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 2-amino-4-methylthiazole (57 mg, 0.50 mmol) in dioxane (1.2 mL) was added trimethylaluminium (2 M in heptane, 251 μl, 0.50 mmol). The resulting red-brown solution was stirred for 1 h at ambient temperature before 2-(5-methyl-3-phenyl-isoxazol-4-ylethynyl)-isonicotinic acid methyl ester (40 mg, 0.13 mmol) was added. The reaction mixture was heated for 2.25 h at 110° C. before cooling to ambient temperature. Water (29 μL) was added and the mixture was stirred for 10 min at ambient temperature. Magnesium sulfate was added and the mixture was filtered over Hyflo®. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=95:5 to 0:100) was followed by separation between hydrochloric acid (1 M, 30 mL) and ethyl acetate (100 mL). The organic layers were washed with brine, dried over sodium sulfate and were concentrated affording the title compound (48 mg, 96%) as an off-white solid. MS: m/e=401.2 [M+H]+.

Workup

  1. additionwas added
  2. temperaturebefore cooling to ambient temperature
  3. filtrationthe mixture was filtered over Hyflo®
  4. concentrationConcentration and purification by chromatography (SiO2, heptane:ethyl acetate=95:5 to 0:100)
  5. customwas followed by separation between hydrochloric acid (1 M, 30 mL) and ethyl acetate (100 mL)
  6. washThe organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationwere concentrated

Sources & evidence

ORD record
ord-1aef2a2ea2694e2493486086c30b2eaa
Source dataset
uspto-grants-2009_06
Patent number
US07544704B2

Reaction notes

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