Реакция #302872

Уравнение реакции

2-aminonicotinic acid methyl ester

ethyl isocyanate

→

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

Выход 12.0%

Растворители

pyridine

Условия реакции

Обработка

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

Методика

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.)

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