反応 #2282960

ord-c00417bebebf448ebc44e10c2d432d8c

溶媒

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    その他Details of an actual preparation
  2. 2
    抽出The mixture was extracted with EtOAc (2×75 mL)
  3. 3
    乾燥the combined organic portions were dried over MgSO4
  4. 4
    その他evaporated
  5. 5
    その他purified by silica gel chromatography (0% to 30% EtOAc/hexanes gradient)

実験手順

Synthesized from tert-butyl [(4aS,5S,7aS)-7a-(5-amino-2-fluorophenyl)-5-trifluoromethyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl]carbamate and 5-fluoromethyl-pyrazine-2-carboxylic acid according to the general procedure. Details of an actual preparation are as follows:-tert-Butyl ((4aS,5S,7aS)-7a-(5-amino-2-fluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)carbamate (500 mg) was dissolved in DCM (10 mL) and 5-fluoromethyl-pyrazine-2-carboxylic acid (223 mg), N,N-diisopropylethylamine (521 mg) and (1H-benzotriazol-1-yloxy)tripyrrolidin-1-yl)phosphonium hexafluorophophate (750 mg) were added. The reaction mixture was stirred at RT for 1 h, and sodium bicarbonate (sat., aq., 50 mL) was added. The mixture was extracted with EtOAc (2×75 mL), the combined organic portions were dried over MgSO4, evaporated and purified by silica gel chromatography (0% to 30% EtOAc/hexanes gradient) to afford the amide (613 mg) as a white solid. The amide was dissolved in DCM (2 mL) and TFA (1 mL) was added. After stirring at RT for 2 h, the reaction mixture was evaporated and sodium bicarbonate (sat., aq., 25 mL) was added. The mixture was extracted with EtOAc (3×25 mL), and the combined organic portions dried over MgSO4 and evaporated to afford the title compound as a white solid

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US08338407B2uspto-grants-2012_12