Reaktion #1951084

Reaktionsgleichung

ammonium hydroxide

2-[4-cyano-2-(4-fluoro-2-methyl-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-2-methyl-3-oxo-butyric acid ethyl ester

H2O

sulfuric acid

→

2-(4-fluoro-2-methyl-phenylamino)-1,6,7-trimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one

Ausbeute 70.0%

Lösungsmittel

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeTo a glass scintillation vial equipped with a magnetic stir bar
2. 2
   workup.ADDITIONwas added to the vial
3. 3
   SonstigeThe vial was sealed with a screw
4. 4
   Sonstigecap
5. 5
   Temperaturto cool to room temperature
6. 6
   workup.ADDITIONThe reaction mixture was then poured onto ice
7. 7
   FiltrationThe resulting precipitate was recovered by filtration
8. 8
   Sonstigefurther purified by trituration with methanol

Vorschrift

To a glass scintillation vial equipped with a magnetic stir bar was added 2-[4-cyano-2-(4-fluoro-2-methyl-phenylamino)-3-methyl-3H-benzoimidazol-5-yl]-2-methyl-3-oxo-butyric acid ethyl ester (0.204 g, 0.483 mmol). A freshly prepared mixture of H2O (3.3 mL), glacial acetic acid (3.3 mL), and concentrated sulfuric acid (3.3 mL) at 60° C. was added to the vial. The vial was sealed with a screw cap and heated to 100° C. in a heating block. After 2.5 hours, the vial was allowed to cool to room temperature and stirred for an additional 12 h. The reaction mixture was then poured onto ice and neutralized by addition of concentrated ammonium hydroxide. The resulting precipitate was recovered by filtration and further purified by trituration with methanol to provide 2-(4-fluoro-2-methyl-phenylamino)-1,6,7-trimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one (0.1188 g, 70%) as a light gray solid. 1H NMR (400 MHz, DMSO-d6+TFA) δ 11.43 (br s, 11H), 10.49 (br s, 1H), 7.70-7.65 (m, 2H), 7.57 (dd, 1H, J1=5.5 Hz, J2=8.6 Hz), 7.37 (dd, 11H, J1=3.1 Hz, J2=9.8 Hz), 7.27 (td, 1H, J1=3.1 Hz, J2=11.7 Hz), 4.23 (s, 3H), 2.32 (app s, 6H), 2.23 (s, 3H); ESMS (m/z): found, 351.

Quelle