反応 #74288

反応方程式

N-((4-(4-cyclopropylpiperazin-1-yl)piperidin-4-yl)methyl)isonicotinamide dihydrochloride

2-(2-(N-cyclopropyl-2-(trifluoromethyl)phenylsulfonamido)-ethoxy)acetic acid

diisopropyl ethylamine

HOBT

EDCI

→

crude product

収率 55.0%

N-((1-(2-(2-(N-Cyclopropyl-2-(trifluoromethyl)phenyl-sulfonamido)ethoxy)acetyl)-4-(4-cyclopropylpiperazin-1-yl)piperidin-4-yl)-methyl)isonicotinamide

収率 55.0%

溶媒

DMF

dichloromethane

dichloromethane

反応条件

後処理

1. 1
   洗浄washed with saturated ammonium chloride solution, brine, saturated sodium bicarbonate and finally again with brine
2. 2
   乾燥The organic layer was dried over sodium sulfate
3. 3
   その他evaporated to dryness under reduced pressure

実験手順

To a solution of 2-(2-(N-cyclopropyl-2-(trifluoromethyl)phenylsulfonamido)-ethoxy)acetic acid AC9 (0.472 mmol) in dichloromethane (10 ml/mmol) was added diisopropyl ethylamine (4 equiv.) at 0° C. followed by the addition of HOBT (1.0 equiv.) and EDCI (1.5 equiv.). The resultant solution was stirred at 25° C. for 15 min. It was again cooled to 0° C. and a solution of N-((4-(4-cyclopropylpiperazin-1-yl)piperidin-4-yl)methyl)isonicotinamide dihydrochloride AM12 (1.2 equiv.) in DMF (2 ml) was added. The reaction mixture was stirred for 16 h at 25° C. The mixture was diluted with dichloromethane, washed with saturated ammonium chloride solution, brine, saturated sodium bicarbonate and finally again with brine. The organic layer was dried over sodium sulfate and evaporated to dryness under reduced pressure to give the crude product which was purified by column chromatography. Yield: 55%. MS, Rt=2.8 min, m/z=693.5 [MH]+.

出典