Reaktion #329494

Reaktionsgleichung

4-methoxy-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine

5-bromo-3-chloro-2-methoxypyridine

sodium tert-butoxide

X-Phos

→

6-(5-chloro-6-methoxy-pyridin-3-yl)-4-methoxy-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine

Ausbeute 19.0%

Lösungsmittel

5/1

heptane tert-butyl methyl ether

toluene tert-butanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe vial was flushed with a stream of argon for 15 sec
2. 2
   Sonstigecapped
3. 3
   TemperaturThe mixture was heated
4. 4
   Temperaturto cool to room temperature
5. 5
   workup.STIRRINGstirred at rt for 5 days
6. 6
   workup.ADDITIONDiluted with CH2Cl2 (10 mL) and water (2 mL)
7. 7
   Filtrationfiltered through a celite pad
8. 8
   SonstigeThe organic phase was separated
9. 9
   Filtrationby filtering through a phase separation tube
10. 10
    Einengenconcentrated in vacuo
11. 11
    SonstigePurified by flash chromatography on silica gel with heptane/EtOAc 100/0 to 0/100

Vorschrift

To a glass vial was added 4-methoxy-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (WO 2008/130481, p 47) (0.273 g, 1.65 mmol), 5-bromo-3-chloro-2-methoxypyridine (0.368 g, 1.65 mmol), sodium tert-butoxide (318 mg, 3.31 mmol), diacetoxypalladium (0.037 g, 0.17 mmol), X-Phos (0.079 g, 0.17 mmol) and anhydrous toluene/tert-butanol, 5/1 (6 mL). The vial was flushed with a stream of argon for 15 sec and capped. The mixture was heated with stirring for 2 h at 110° C. then allowed to cool to room temperature and stirred at rt for 5 days. Diluted with CH2Cl2 (10 mL) and water (2 mL), filtered through a celite pad. The organic phase was separated by filtering through a phase separation tube and concentrated in vacuo. Purified by flash chromatography on silica gel with heptane/EtOAc 100/0 to 0/100 to give 6-(5-chloro-6-methoxy-pyridin-3-yl)-4-methoxy-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine as a yellow solid (95 mg, 19% yield) LCMS: [M+H]+=307.0/308.9, Rt(3)=1.62 min.

Quelle