반응 #74284

반응 방정식

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

수율 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

수율 55.0%

용매

dichloromethane

dichloromethane

DMF

반응 조건

후처리

1. 1
   온도It was again cooled to 0° C.
2. 2
   workup.STIRRINGThe reaction mixture was stirred for 16 h at 25° C
3. 3
   세척washed with saturated ammonium chloride solution, brine, saturated sodium bicarbonate and finally again with brine
4. 4
   건조The organic layer was dried over sodium sulfate
5. 5
   기타evaporated to dryness under reduced pressure

실험 절차

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]+.

출처