Isopropylamine → 2-[(E)-2-(3-Butyl-5-methyl-isoxazol-4-yl)-vinyl]-4-methyl-thiazole-5-carboxylic acid isopropylamide

HRID 1923608Notes

Reaction equation

HRID 1923608 reaction equation
[CH:1]([NH2:4])([CH3:3])[CH3:2].C[Al](C)C.C[O:10][C:11]([C:13]1[S:17][C:16](/[CH:18]=[CH:19]/[C:20]2[C:21]([CH2:26][CH2:27][CH2:28][CH3:29])=[N:22][O:23][C:24]=2[CH3:25])=[N:15][C:14]=1[CH3:30])=O>O1CCOCC1.C1(C)C=CC=CC=1>[CH:1]([NH:4][C:11]([C:13]1[S:17][C:16](/[CH:18]=[CH:19]/[C:20]2[C:21]([CH2:26][CH2:27][CH2:28][CH3:29])=[N:22][O:23][C:24]=2[CH3:25])=[N:15][C:14]=1[CH3:30])=[O:10])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 6363IsopropylamineHCID 16682925TrimethylaluminumHCID 666436512-[(E)-2-(3-Butyl-5-methyl-isoxazol-4-yl)-vinyl]-4-methyl-thiazole-5-carboxylic acid methyl ester

Product 1

HCID 497809302-[(E)-2-(3-Butyl-5-methyl-isoxazol-4-yl)-vinyl]-4-methyl-thiazole-5-carboxylic acid isopropylamideYield 68%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
90 °C

Procedure

To a stirred solution of isopropylamine (59 mg, 1.0 mmol) in dioxane (2 mL) under argon and at room temperature was added trimethylaluminium (0.50 mL of a 2M solution in toluene, 1.0 mmol). After 1 h, a solution of 2-[(E)-2-(3-butyl-5-methyl-isoxazol-4-yl)-vinyl]-4-methyl-thiazole-5-carboxylic acid methyl ester (80 mg, 0.25 mmol) in dioxane (2 mL) was added and the reaction mixture warmed to 90° C. After 48 h, the reaction mixture was cooled, quenched with Seignettes's salt solution (2 mL) and water (2 mL), then extracted with ethyl acetate. The combined organic extracts were dried, filtered and concentrated. Purification by chromatography (silica, 10 to 80% ethyl acetate in heptane) gave the title compound (59 mg, 68%) as pale yellow solid. MS: m/e=348.0 [M+H]+.

Workup

  1. waitAfter 48 h
  2. temperaturethe reaction mixture was cooled
  3. customquenched with Seignettes's salt solution (2 mL) and water (2 mL)
  4. extractionextracted with ethyl acetate
  5. customThe combined organic extracts were dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by chromatography (silica, 10 to 80% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-d65ea5a1853a4a9088bb0068f79130b6
Source dataset
uspto-grants-2012_05
Patent number
US08178522B2

Reaction notes

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