Reaction #74284

Reaction equation

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

Yield 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

Yield 55.0%

Solvents

dichloromethane

dichloromethane

DMF

Conditions

Workup

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

Procedure

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]+.

Source