反应 #74284

反应方程式

2-(2-(2-chloro-N-cyclopropyl-6-methylphenylsulfonamido)-ethoxy)acetic acid

diisopropyl ethylamine

N-((4-(4-cyclopropyl-piperazin-1-yl)piperidin-4-yl)methyl)isonicotinamide dihydrochloride

HOBT

EDCI

→

crude product

收率 55.0%

N-((1-(2-(2-(2-Chloro-N-cyclopropyl-6-methylphenyl-sulfonamido)ethoxy)acetyl)-4-(4-cyclopropylpiperazin-1-yl)piperidin-4-yl)-methyl)isonicotinamide

收率 55.0%

溶剂

dichloromethane

dichloromethane

DMF

反应条件

后处理

1. 1
   温度It was again cooled to 0° C.
2. 2
   workup.STIRRINGThe reaction mixture was stirred for 16 h at 25° C
3. 3
   洗涤washed with saturated ammonium chloride solution, brine, saturated sodium bicarbonate and finally again with brine
4. 4
   干燥The organic layer was dried over sodium sulfate
5. 5
   其他evaporated to dryness under reduced pressure

实验过程

To a solution of 2-(2-(2-chloro-N-cyclopropyl-6-methylphenylsulfonamido)-ethoxy)acetic acid AC8 (0.225 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 resulting solution was stirred at 25° C. for 15 min. It was again cooled to 0° C. and a solution of N-((4-(4-cyclopropyl-piperazin-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=673.4 [MH]+.

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