Reacción #471829

Ecuación de reacción

Methyl 4-((1-(tert-butoxycarbonyl)piperidin-4-yl)methylamino)-6-chloronicotinate

5-methylpyrazin-2-amine

cesium carbonate

4,5-bis(diphenyl phosphino)-9,9-dimethylxanthene

→

methyl 6-(5-methylpyrazin-2-ylamino)-4-(1-Boc-piperidin-4-ylmethylamino)nicotinate

Rendimiento 33.3%

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas capped
2. 2
   Otroflushed with nitrogen
3. 3
   workup.ADDITIONAnhydrous toluene (1.35 mL) was added
4. 4
   Otronitrogen was bubbled through the stirred solution for 10 minutes
5. 5
   TemperaturaThe solution was cooled
6. 6
   workup.ADDITIONdiluted with dichloromethane-methanol
7. 7
   LavadoThe resin was washed with methanol
8. 8
   ConcentraciónThe basic fractions were concentrated
9. 9
   Otrothe residue was purified by preparative TLC
10. 10
    Lavadoeluting with 10% methanol-dichloromethane)

Procedimiento

Methyl 4-((1-(tert-butoxycarbonyl)piperidin-4-yl)methylamino)-6-chloronicotinate (90 mg, 0.23 mmol), 5-methylpyrazin-2-amine (38 mg, 0.35 mmol, as described in Itoh et al., 2002), cesium carbonate (153 mg, 0.47 mmol), 4,5-bis(diphenyl phosphino)-9,9-dimethylxanthene (11 mg, 8 mol %), and tris(dibenzylidene acetone)dipalladium chloroform complex (10 mg, 4 mol %) were added to an oven-dried microwave reactor vial (2 mL) which was capped and flushed with nitrogen. Anhydrous toluene (1.35 mL) was added and nitrogen was bubbled through the stirred solution for 10 minutes. The mixture was heated at 130° C. for 30 minutes by microwave irradiation. The solution was cooled, diluted with dichloromethane-methanol and adsorbed onto a 2 g (solute SCX-II column. The resin was washed with methanol, then with 2M ammonia in methanol. The basic fractions were concentrated and the residue was purified by preparative TLC, eluting with 10% methanol-dichloromethane) to give methyl 6-(5-methylpyrazin-2-ylamino)-4-(1-Boc-piperidin-4-ylmethylamino)nicotinate (35 mg) as a light green powder.

Fuente