N'-羟基-2-(三氟甲基)苯甲亚胺

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under argon, 95 mg (0.18 mmol) of benzotriazol-1-yloxy-tris(pyrrolidino)phosphonium hexafluorophosphate were added to a solution of 56 mg (0.15 mmol) of [3-(5-chloro-2-thienyl)-4-(2-fluorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetic acid [preparation according to WO 2007/134862 Example 154A] and 32 μl (0.18 mmol) of N,N-diisopropylethylamine in 1.5 ml of dry DMF. After 20 min of stirring, 34 mg (0.17 mmol) of N′-hydroxy-2-(trifluoromethyl)benzene-carboximidamide were added. The mixture was then stirred at RT for 16 h. For work-up, 10 ml of water were added and the mixture was extracted three times with in each case 10 ml of ethyl acetate. The combined organic phases were washed with in each case 10 ml of water and saturated sodium chloride solution, filtered through Extrelut and concentrated under reduced pressure. The residue was dissolved in 2 ml of DMF and stirred in a microwave oven at 250° C. for 15 min. After cooling, the solvent was removed under reduced pressure on a rotary evaporator and the crude product was chromatographed on silica gel (mobile phase: cyclohexane/ethyl acetate 4:1). This gave 60 mg (72% of theory) of the target compound as a yellow resin. The mixture was then stirred at RT for 16 h the mixture was extracted three times with in each case 10 ml of ethyl acetate The combined organic phases were washed with in each case 10 ml of water and saturated sodium chloride solution filtered through Extrelut concentrated under reduced pressure The residue was dissolved in 2 ml of DMF stirred in a microwave oven at 250° C. for 15 min After cooling the solvent was removed under reduced pressure on a rotary evaporator the crude product was chromatographed on silica gel (mobile phase: cyclohexane/ethyl acetate 4:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under argon, 95 mg (0.18 mmol) of benzotriazol-1-yloxy-tris(pyrrolidino)phosphonium hexafluorophosphate were added to a solution of 56 mg (0.15 mmol) of [3-(5-chloro-2-thienyl)-4-(2-fluorobenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl]acetic acid [preparation according to WO 2007/134862 Example 154A] and 32 μl (0.18 mmol) of N,N-diisopropylethylamine in 1.5 ml of dry DMF. After 20 min of stirring, 34 mg (0.17 mmol) of N′-hydroxy-2-(trifluoromethyl)benzene-carboximidamide were added. The mixture was then stirred at RT for 16 h. For work-up, 10 ml of water were added and the mixture was extracted three times with in each case 10 ml of ethyl acetate. The combined organic phases were washed with in each case 10 ml of water and saturated sodium chloride solution, filtered through Extrelut and concentrated under reduced pressure. The residue was dissolved in 2 ml of DMF and stirred in a microwave oven at 250° C. for 15 min. After cooling, the solvent was removed under reduced pressure on a rotary evaporator and the crude product was chromatographed on silica gel (mobile phase: cyclohexane/ethyl acetate 4:1). This gave 60 mg (72% of theory) of the target compound as a yellow resin. The mixture was then stirred at RT for 16 h the mixture was extracted three times with in each case 10 ml of ethyl acetate The combined organic phases were washed with in each case 10 ml of water and saturated sodium chloride solution filtered through Extrelut concentrated under reduced pressure The residue was dissolved in 2 ml of DMF stirred in a microwave oven at 250° C. for 15 min After cooling the solvent was removed under reduced pressure on a rotary evaporator the crude product was chromatographed on silica gel (mobile phase: cyclohexane/ethyl acetate 4:1)