Reacción #1072293

Ecuación de reacción

triethylamine

dimethylaminopyridine

pivaloyl chloride

triethylamine

9

(7S,8R,9R)-8-Hydroxy-7-[2-(2-methoxyethoxy)ethoxy]2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridine

dimethylaminopyridine

pivaloyl chloride

dichloromethane

(8R,9R)-8-hydroxy-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one

dichloromethane

→

title compound

(7R,8R,9R)-10-Acetyl-3-chloro-7-(2-methoxyethoxy)-2-methyl-9-phenyl-8-pivaloyloxy-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturawarmed up to 25° C.
2. 2
   workup.STIRRINGstirred for further 24 h
3. 3
   workup.STIRRINGis stirred for 18 h at 25° C
4. 4
   OtroSubsequently the reaction is quenching
5. 5
   workup.ADDITIONby adding of water (100 ml)
6. 6
   OtroThe organic layer is separated
7. 7
   Lavadowashed with ammonia solution
8. 8
   Lavadowashed with water two times
9. 9
   Secadodried over sodium sulphate
10. 10
    Otroevaporated in vacuo
11. 11
    OtroThe crude product is crystallised from 2-propanol

Procedimiento

To a of 0° C. cooled solution of 10.5 g (35.8 mmol) (8R,9R)-8-hydroxy-2-methyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-7-one in dichloromethane (110 ml) is added 5.70 ml (41.2 mmol) triethylamine, 0.22 g (1.80 mmol) dimethylaminopyridine and 5.10 ml (41.2 mmol) pivaloyl chloride dissolved in dichloromethane (10 ml). The reaction is stirred for 2 h at 0° C. and warmed up to 25° C. and stirred for further 24 h. Afterwards 5.70 ml (41.2 mmol) triethylamine, 0.22 9 (1.80 mmol) dimethylaminopyridine and 5.10 ml (41.2 mmol) pivaloyl chloride are added to this mixture and it is stirred for 18 h at 25° C. Subsequently the reaction is quenching by adding of water (100 ml). The organic layer is separated, washed with ammonia solution, washed with water two times, dried over sodium sulphate and evaporated in vacuo. The crude product is crystallised from 2-propanol to provide 12.1 g (32.06 mmol/90%) of the title compound as a colourless solid with a melting point of 145-147° C. (2-propanol).

Fuente