Reaction #46601

Reaction equation

(E)-3-[6-[N-(methoxycarbonylmethyl)amino]pyridin-3-yl]acrylic acid hydrochloride salt

2-methyl-3-(methylaminomethyl)indole

Et3N

HOBt H2O

EDC

→

title compound

Yield 73.0%

(E)-3-[6-[N-(methoxycarbonylmethyl)amino]pyridin-3-yl]-N-methyl-N-(2-methyl-1H-indol-3-ylmethyl)acrylamide

Yield 73.0%

Solvents

DMF CH2Cl2

Conditions

Workup

1. 1
   Concentrationwas concentrated to dryness
2. 2
   Washthe solution was washed with H2O
3. 3
   Dryingbrine, dried (Na2SO4)
4. 4
   Concentrationconcentrated under vacuum
5. 5
   OtherThe remaining residue was purified by flash chromatography on silica gel (4% MeOH/CHCl3)

Procedure

To a stirred solution of (E)-3-[6-[N-(methoxycarbonylmethyl)amino]pyridin-3-yl]acrylic acid hydrochloride salt (2.0 g, 7.3 mmole) in 1:1 DMF/CH2Cl2 (100 mL) was added 2-methyl-3-(methylaminomethyl)indole (1.3 g, 7.5 mmole), Et3N (2.1 mL, 15 mmole), and HOBt H2O (1.0 g, 7.4 mmole), followed by EDC (1.4 g, 7.3 mmole). After stirring at room temperature for 18 h the reaction was concentrated to dryness. The residue was taken up in EtOAc, and the solution was washed with H2O then brine, dried (Na2SO4), and concentrated under vacuum. The remaining residue was purified by flash chromatography on silica gel (4% MeOH/CHCl3) to give the title compound (2.08 g, 73%) as an off-white solid: MS (ES) m/e 393.2 (M+H)+.

Source