Reaction #46596

Reaction equation

6-bromo-3,4-dihydro-1H-1,8-naphthyridin-2-one

N-(1H-indol-3-ylmethyl)-N-methylacrylamide

tri-ortho-tolylphosphine

diisopropylethylamine

→

title compound

Yield 37.0%

(E)-N-(1H-indol-3-ylmethyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide

Yield 37.0%

Solvents

propionitrile

Conditions

Workup

1. 1
   Temperaturewas heated
2. 2
   Temperatureto reflux under N2 overnight
3. 3
   FiltrationThe dark mixture was filtered through a pad of Celite®
4. 4
   Washthe filter pad was rinsed with acetonitrile (250 mL)
5. 5
   ConcentrationThe filtrate was concentrated in vacuo
6. 6
   Otherthe residue was purified by flash chromatography on silica gel (10% MeOH/CHCl3)

Procedure

A solution of 6-bromo-3,4-dihydro-1H-1,8-naphthyridin-2-one (0.64 g, 2.80 mmole), N-(1H-indol-3-ylmethyl)-N-methylacrylamide (0.60 g, 2.80 mmole), Pd(OAc)2 (0.06 g, 0.28 mmole), tri-ortho-tolylphosphine (0.17 g, 0.56 mmole) and diisopropylethylamine (0.73 mL, 4.2 mmole) in propionitrile (50 mL) was deoxygenated, then was heated to reflux under N2 overnight. The dark mixture was filtered through a pad of Celite®, and the filter pad was rinsed with acetonitrile (250 mL). The filtrate was concentrated in vacuo, and the residue was purified by flash chromatography on silica gel (10% MeOH/CHCl3). The title compound (0.37 g, 37%) was obtained as a light yellow solid after drying in vacuo: MS (ES) m/e 361 (M+H)+.

Source