4-Aminotetrahydropyran → 2-[(e)-2-(5-Methyl-3-phenyl-isoxazol-4-yl)-vinyl]-thiazole-5-carboxylic acid(tetra-hydro-pyran-4-yl)-amide

HRID 1923561Notes

Reaction equation

HRID 1923561 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.C[Al](C)C.C([O:14][C:15]([C:17]1[S:21][C:20](/[CH:22]=[CH:23]/[C:24]2[C:25]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[N:26][O:27][C:28]=2[CH3:29])=[N:19][CH:18]=1)=O)C>O1CCOCC1.C1(C)C=CC=CC=1>[O:5]1[CH2:6][CH2:7][CH:2]([NH:1][C:15]([C:17]2[S:21][C:20](/[CH:22]=[CH:23]/[C:24]3[C:25]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[N:26][O:27][C:28]=3[CH3:29])=[N:19][CH:18]=2)=[O:14])[CH2:3][CH2:4]1

Participants

6

Reactant 3

HCID 4192234-AminotetrahydropyranHCID 16682925TrimethylaluminumHCID 66643683HCID 66643683, compound

Product 1

HCID 497818072-[(e)-2-(5-Methyl-3-phenyl-isoxazol-4-yl)-vinyl]-thiazole-5-carboxylic acid(tetra-hydro-pyran-4-yl)-amideYield 59%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
90 °C

Procedure

To a stirred solution of 4-aminotetrahydropyran (123 mg, 1.22 mmol) in dioxane (3 mL) under argon and at room temperature was added trimethylaluminium (0.6 mL of a 2M solution in toluene, 1.2 mmol). After 1 h, a solution of 2-[(E)-2-(5-methyl-3-phenyl-isoxazol-4-yl)-vinyl]-thiazole-5-carboxylic acid ethyl ester (50 mg, 0.15 mmol) in dioxane (3 mL) was added and the reaction mixture heated at 90° C. for 3 h. The reaction mixture was then 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 2.5% methanol in dichloromethane) gave the title compound (34 mg, 59%) as a white solid. MS: m/e=396.3 [M+H]+.

Workup

  1. temperatureThe reaction mixture was then cooled
  2. customquenched with ice water
  3. extractionextracted with dichloromethane
  4. washThe combined extracts were washed with Seignette's salt solution
  5. customthen dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by chromatography (silica, 0 to 2.5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-e81960e92c454ae1a7622ce43806fe75
Source dataset
uspto-grants-2012_05
Patent number
US08178522B2

Reaction notes

Loading…