Isopropylamine → 5-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridine-2-carboxylic acid isopropylamide

HRID 1962950Notes

Reaction equation

HRID 1962950 reaction equation
[CH:1]([NH2:4])([CH3:3])[CH3:2].C[Al](C)C.C([O:11][C:12]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]2[C:23]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:24][O:25][C:26]=2[CH3:27])=[CH:16][N:15]=1)=O)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>O1CCOCC1.O>[CH:1]([NH:4][C:12]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]2[C:23]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:24][O:25][C:26]=2[CH3:27])=[CH:16][N:15]=1)=[O:11])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6363IsopropylamineHCID 9357Potassium Sodium TartrateHCID 16682925TrimethylaluminumHCID 666443955-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridine-2-carboxylic acid ethyl ester

Product 1

HCID 498030185-(5-Methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridine-2-carboxylic acid isopropylamideYield 95.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a stirred solution of isopropylamine (98 mg, 1.66 mmol) in dioxane (3 mL) was added dropwise a trimethylaluminium (0.83 mL, 2 M solution in toluene, 1.66 mmol) and the resulting solution stirred under argon for 30 min. A solution of 5-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-pyridine-2-carboxylic acid ethyl ester (140 mg, 0.41 mmol) in dioxane (3 mL) was then added and the resulting solution stirred under argon for a further 20 h at 85° C. The reaction mixture was cooled and Seignette salt solution (2 mL) and water (2 mL) were added. The reaction mixture was extracted with ethyl acetate (3×20 mL). The combined organic layers were dried, filtered and concentrated in vacuo. Purification by chromatography (silica, 0 to 6% methanol in dichloromethane) gave the title compound (138 mg, 95%) as a light yellow solid. MS: m/e=352.3 [M+H]+.

Workup

  1. stirringthe resulting solution stirred under argon for a further 20 h at 85° C
  2. temperatureThe reaction mixture was cooled
  3. extractionThe reaction mixture was extracted with ethyl acetate (3×20 mL)
  4. customThe combined organic layers were dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by chromatography (silica, 0 to 6% methanol in dichloromethane)

Sources & evidence

ORD record
ord-174be4c4577f4b239579c854d19e47eb
Source dataset
uspto-grants-2013_04
Patent number
US08415379B2

Reaction notes

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