反応 #302872

反応方程式

2-aminonicotinic acid methyl ester

ethyl isocyanate

→

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

収率 12.0%

溶媒

pyridine

反応条件

後処理

1. 1
   温度was refluxed for 23 hours
2. 2
   その他The pyridine was removed under reduced pressure
3. 3
   workup.ADDITIONthe residue was treated with 370 ml methanol
4. 4
   温度The mixture was refluxed for 10 minutes
5. 5
   温度The mixture is further cooled to 0° C.
6. 6
   その他to crystallize over night
7. 7
   その他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)
8. 8
   その他The isolated 3-ethyl-1H-pyrido[2,3-d]pyrimidine-2,4-dione was recrystallized from dimethyl formamide
9. 9
   その他isolated by filtration
10. 10
    洗浄washed twice with ethanol and twice with tert butyl methyl ether
11. 11
    その他The isolated compound was further recrystallized from methanol
12. 12
    その他A first crop of 2.5 g was isolated
13. 13
    その他Upon concentration of the filtrate a second crop of 0.5 g was isolated

実験手順

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.)

出典