Reaction #156555

Reaction equation

HCl

2-(4-Chloro-2-methoxypyridin-3-yl)imidazo[4,5-f]isoindole-5,7(1H, 6H)-dione

1-(2,3,5-trifluorophenyl)propan-2-amine

N,N-diisopropylethylamine

→

2-(2-oxo-4-(1-(2,3,5-trifluorophenyl)propan-2-ylamino)-1,2-dihydropyridin-3-yl)-6-(1-(2,3,5-trifluorophenyl)propan-2-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione

Yield 76.5%

Solvents

1,4-dioxane

n-butanol

Conditions

Workup

1. 1
   Otherat rt
2. 2
   OtherThen, the volatile was removed
3. 3
   Otherto give a yellow-brown solid
4. 4
   workup.STIRRINGThe reaction mixture was stirred
5. 5
   Temperatureheated
6. 6
   Temperatureto reflux overnight under argon
7. 7
   OtherThen, volatiles were removed under reduced pressure
8. 8
   OtherThe residue solid was purified by column chromatography (silica-gel, CH2Cl2/MeOH=9/1 v/v)
9. 9
   Otherto give a yellow-brown solid product, 0.78 g, 76.5% yield

Procedure

2-(4-Chloro-2-methoxypyridin-3-yl)imidazo[4,5-f]isoindole-5,7(1H, 6H)-dione (0.522 g, 1.59 mmol) was dissolved in 10 mL of 1,4-dioxane and 5 mL of concentrated HCl at rt. The reaction mixture was stirred at rt overnight. Then, the volatile was removed to give a yellow-brown solid. This solid was mixed with 1-(2,3,5-trifluorophenyl)propan-2-amine (0.30 g, 1.59 mmol), N,N-diisopropylethylamine (1.10 g, 9.54 mmol) and n-butanol (20 mL) in a flask. The reaction mixture was stirred and heated to reflux overnight under argon. Then, volatiles were removed under reduced pressure. The residue solid was purified by column chromatography (silica-gel, CH2Cl2/MeOH=9/1 v/v) to give a yellow-brown solid product, 0.78 g, 76.5% yield. MS: 640.2 [M+H]+. 1H NMR (DMSO-d6, 500 MHz): δ 13.38 (s, 1H), 11.32-11.29 (m, 1H), 10.94-10.91 (m, 1H), 8.06 (s, 1H), 7.84 (s, 1H), 7.64-7.60 (m, 1H), 7.37-7.34 (m, 1H), 7.08-6.99 (m, 2H), 6.14 (d, 1H, J=7.5 Hz), 4.50 (m, 1H), 4.18 (m, 1H), 3.37-3.32 (m, 1H), 3.15-3.01 (m, 3H), 1.57 (d, 3H, J=7.0 Hz), 1.35 (d, 3H, J=6.5 Hz).

Source