Ethyl isocyanate → HCID 12813225, compound

HRID 215690Notes

Reaction equation

HRID 215690 reaction equation
CO[C:3](=[O:11])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][C:5]=1[NH2:10].[CH2:12]([N:14]=[C:15]=[O:16])[CH3:13]>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[CH2:12]([N:14]1[C:3](=[O:11])[C:4]2[CH:9]=[CH:8][CH:7]=[N:6][C:5]=2[NH:10][C:15]1=[O:16])[CH3:13]

Participants

5

Reactant 2

HCID 8022Ethyl isocyanateHCID 351633Methyl 2-aminopyridine-3-carboxylate

Product 1

HCID 12813225HCID 12813225, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

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.)

Workup

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

Sources & evidence

ORD record
ord-eb87c30470474660b78b56d34a127255
Source dataset
uspto-grants-2012_06
Patent number
US08192918B2

Reaction notes

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