Isopropylamine → 4-Methyl-2-[2-(5-methyl-3-phenyl-isoxazol-4-yl)-ethyl]-thiazole-5-carboxylic acid iso-propylamide

HRID 1923489Notes

Reaction equation

HRID 1923489 reaction equation
[CH:1]([NH2:4])([CH3:3])[CH3:2].C[Al](C)C.[CH3:9][C:10]1[N:11]=[C:12]([CH2:18][CH2:19][C:20]2[C:21]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[N:22][O:23][C:24]=2[CH3:25])[S:13][C:14]=1[C:15](O)=[O:16]>O1CCOCC1.C1(C)C=CC=CC=1>[CH:1]([NH:4][C:15]([C:14]1[S:13][C:12]([CH2:18][CH2:19][C:20]2[C:21]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[N:22][O:23][C:24]=2[CH3:25])=[N:11][C:10]=1[CH3:9])=[O:16])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 6363IsopropylamineHCID 16682925TrimethylaluminumHCID 66643564HCID 66643564, compound

Product 1

HCID 497824864-Methyl-2-[2-(5-methyl-3-phenyl-isoxazol-4-yl)-ethyl]-thiazole-5-carboxylic acid iso-propylamideYield 54.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
90 °C

Procedure

To a stirred solution of isopropylamine (216 mg, 3.65 mmol) in dioxane (4 mL) under argon and at room temperature was added trimethylaluminium (1.83 mL of a 2M solution in toluene, 3.7 mmol). After 1 h, a solution of 4-methyl-2-[2-(5-methyl-3-phenyl-isoxazol-4-yl)-ethyl]-thiazole-5-carboxylic acid (300 mg, 0.91 mmol) in dioxane (4 mL) was added and the reaction mixture warmed to 90° C. After 4 h, the reaction mixture was cooled, quenched with ice water and extracted with dichloromethane. The combined extracts were washed with Seignette's salt solution then dried, filtered, and concentrated. Purification by chromatography (silica, 0 to 10% methanol in dichloromethane) gave the title compound (182 mg, 54%) as a light yellow gum. MS: m/e=370.1 [M+H]+.

Workup

  1. waitAfter 4 h
  2. temperaturethe reaction mixture was cooled
  3. customquenched with ice water
  4. extractionextracted with dichloromethane
  5. washThe combined extracts were washed with Seignette's salt solution
  6. customthen dried
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by chromatography (silica, 0 to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-bf483c2a34884c1c97c89b3607099cf5
Source dataset
uspto-grants-2012_05
Patent number
US08178522B2

Reaction notes

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