Réaction #302872

Équation de réaction

2-aminonicotinic acid methyl ester

ethyl isocyanate

→

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

Rendement 12.0%

Solvants

pyridine

Conditions de réaction

Traitement

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

Mode opératoire

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.)

Source