反応 #72255

反応方程式

cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-N-(2-cyanoethyl)-4-methyl-1,3-thiazole-5-carboxylic acid amide

triphenylphosphine

diisopropyl azodicarboxylate

trimethylsilyl azide

→

title compound

収率 41.0%

cis(±)-4-Chloro-N-(1-{5-[1-(2-cyanoethyl)-1H-tetrazol-5-yl]-4-methyl-1,3-thiazol-2-yl}-3-methoxypiperidin-4-yl)-5-ethyl-1H-imidazole-2-carboxylic acid amide

収率 41.0%

溶媒

THF

ethyl acetate

反応条件

後処理

1. 1
   workup.STIRRINGby stirring at 30° C. for four days
2. 2
   洗浄The organic layer was washed with water and brine
3. 3
   乾燥dried over anhydrous magnesium sulfate
4. 4
   濃縮concentrated under reduced pressure
5. 5
   その他The residue was purified by silica gel column chromatography (elution solvent: methanol/ethyl acetate=0/10, 2/8) and preparative thin layer chromatography (developing solvent: ethyl acetate/hexane=10/1)

実験手順

THF (2 mL) was added to cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-N-(2-cyanoethyl)-4-methyl-1,3-thiazole-5-carboxylic acid amide obtained in Example (261a) (36 mg, 0.08 mmol). While the mixture was stirred, triphenylphosphine (124 mg, 0.47 mmol), diisopropyl azodicarboxylate (0.24 mL, 0.45 mmol, 1.9 M solution in toluene) and trimethylsilyl azide (7.3 g, 55.4 mmol) were added, followed by stirring at 30° C. for four days. The reaction solution was diluted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: methanol/ethyl acetate=0/10, 2/8) and preparative thin layer chromatography (developing solvent: ethyl acetate/hexane=10/1) to obtain 16 mg of the title compound as a white solid (41%).

出典