Reaktion #1951090

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

water

sulfuric acid

→

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

Ausbeute 89.0%

Lösungsmittel

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeTo a 500 mL round-bottom flask equipped with a magnetic stir-bar
2. 2
   SonstigeThe flask was fitted with a reflux condenser
3. 3
   Temperaturto cool to room temperature
4. 4
   workup.ADDITIONThe mixture was then poured onto ice
5. 5
   Temperaturwhile maintaining a temperature of less than 15° C
6. 6
   SonstigeThe resulting precipitate was isolated by filtration
7. 7
   Waschenwashed with several volumes of water
8. 8
   workup.WAITThe solid was then slurried in methanol for 1 hour
9. 9
   Filtrationfiltered
10. 10
    WaschenThe isolated solid was washed with cold methanol until the filtrate

Vorschrift

To a 500 mL round-bottom flask 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 (8.25 g, 1.95 mmole), followed by a freshly prepared mixture of water (25 mL), acetic acid (25 mL), and concentrated sulfuric acid (25 mL) at 60° C. The flask was fitted with a reflux condenser and heated to a bath temperature of 100° C. under a nitrogen atmosphere. After 5 hours, the reaction was allowed to cool to room temperature, and stirred for an additional 14 hours. The mixture was then poured onto ice and brought to a slightly basic pH by careful addition of concentrated ammonium hydroxide, while maintaining a temperature of less than 15° C. The resulting precipitate was isolated by filtration, and washed with several volumes of water. The solid was then slurried in methanol for 1 hour, and filtered. The isolated solid was washed with cold methanol until the filtrate was colorless, to provide 2-(4-fluoro-2-methyl-phenylamino)-1,6,7-trimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one (6.11 g, 89%) as a light gray solid. 1H NMR (400 MHz, DMSO-d6+TFA) δ 11.43 (br s, 1H), 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, 1H, 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): 351 (M+1)+.

Quelle