Reaktion #302872

Reaktionsgleichung

2-aminonicotinic acid methyl ester

ethyl isocyanate

→

3-ethyl-1H-pyrido[2,3-d]pyrimidine-2,4-dione

Ausbeute 12.0%

Lösungsmittel

pyridine

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas refluxed for 23 hours
2. 2
   SonstigeThe pyridine was removed under reduced pressure
3. 3
   workup.ADDITIONthe residue was treated with 370 ml methanol
4. 4
   TemperaturThe mixture was refluxed for 10 minutes
5. 5
   TemperaturThe mixture is further cooled to 0° C.
6. 6
   Sonstigeto crystallize over night
7. 7
   SonstigeThe crude 3-ethyl-1H-pyrido[2,3-d]pyrimidine-2,4-dione was further purified by preparative column chromatography on straight phase silica (eluent:chloroform:methanol 9:1)
8. 8
   SonstigeThe isolated 3-ethyl-1H-pyrido[2,3-d]pyrimidine-2,4-dione was recrystallized from dimethyl formamide
9. 9
   Sonstigeisolated by filtration
10. 10
    Waschenwashed twice with ethanol and twice with tert butyl methyl ether
11. 11
    SonstigeThe isolated compound was further recrystallized from methanol
12. 12
    SonstigeA first crop of 2.5 g was isolated
13. 13
    SonstigeUpon concentration of the filtrate a second crop of 0.5 g was isolated

Vorschrift

A mixture of 20.00 g (0.132 mol) of 2-aminonicotinic acid methyl ester, 17.67 g (0.248 mol) ethyl isocyanate and 2 g (0.016 mol) 4-dimethylaminopyridine in dry pyridine was refluxed for 23 hours. The pyridine was removed under reduced pressure and the residue was treated with 370 ml methanol. The mixture was refluxed for 10 minutes and allowed to cool down first to room temperature. The mixture is further cooled to 0° C. and the crude 3-ethyl-1H-pyrido[2,3-d]pyrimidine-2,4-dione was allowed to crystallize over night. The crude 3-ethyl-1H-pyrido[2,3-d]pyrimidine-2,4-dione was further purified by preparative column chromatography on straight phase silica (eluent:chloroform:methanol 9:1). The isolated 3-ethyl-1H-pyrido[2,3-d]pyrimidine-2,4-dione was recrystallized from dimethyl formamide, isolated by filtration and washed twice with ethanol and twice with tert butyl methyl ether. The isolated compound was further recrystallized from methanol. A first crop of 2.5 g was isolated. Upon concentration of the filtrate a second crop of 0.5 g was isolated. Both fractions were pooled and finally 3.00 g (12%) of 3-ethyl-1H-pyrido[2,3-d]pyrimidine-2,4-dione was isolated (m.p. 240-1° C.)

Quelle