Reacción #302872

Ecuación de reacción

2-aminonicotinic acid methyl ester

ethyl isocyanate

→

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

Rendimiento 12.0%

Disolventes

pyridine

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturawas refluxed for 23 hours
2. 2
   OtroThe pyridine was removed under reduced pressure
3. 3
   workup.ADDITIONthe residue was treated with 370 ml methanol
4. 4
   TemperaturaThe mixture was refluxed for 10 minutes
5. 5
   TemperaturaThe mixture is further cooled to 0° C.
6. 6
   Otroto crystallize over night
7. 7
   OtroThe 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
   OtroThe isolated 3-ethyl-1H-pyrido[2,3-d]pyrimidine-2,4-dione was recrystallized from dimethyl formamide
9. 9
   Otroisolated by filtration
10. 10
    Lavadowashed twice with ethanol and twice with tert butyl methyl ether
11. 11
    OtroThe isolated compound was further recrystallized from methanol
12. 12
    OtroA first crop of 2.5 g was isolated
13. 13
    OtroUpon concentration of the filtrate a second crop of 0.5 g was isolated

Procedimiento

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.)

Fuente