4-Aminopyridine → HCID 14672910, compound

HRID 1638696Notes

Reaction equation

HRID 1638696 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(N=C=NC2CCCCC2)CCCCC1.[NH2:31][C:32]1[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=1>CN(C)C=O>[CH2:1]([O:8][C:9]([NH:11][CH2:12][C:13]([NH:31][C:32]1[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=1)=[O:15])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 17274-AminopyridineHCID 10868DicyclohexylcarbodiimideHCID 14349Benzyloxycarbonylglycine

Product 1

HCID 14672910HCID 14672910, compoundYield 71.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

36 g of N-benzyloxycarbonyl glycine was dissolved in 400 ml of dimethylformamide and the solution was cooled to -8° C., to which 56.8 g of dicylohexylcarbodiimide dissolved in 50 ml of dimethylformamide was added while maintaining the temperature at -8° to -6° C. After stirring at -6° to -3° C. for 15 minutes, 17 g of 4-aminopyridine was added at -3° to -1° C. The reaction liquid was allowed to stand so as to rise its temperature to room temperature over 2 hours and stirred at room temperature overnight. Then, dicyclohexylurea was filtered off and dimethylformamide was distilled off under reduced pressure. The residue was purified through the chromatography on silica gel (silica gel 1 kg; chloroform-methanol (3%→6%) as the eluent) and recrystallized from methanol-ethyl acetate to obtain 35.2 g of 4-[(N-benzyloxycarbonyl glycyl)amino]pyridine having the melting point of 154° to 156° C. This was dissolved in 1 l of methanol and 2.3 g of palladium black was added thereto followed by subjecting to the catalytic hydrogenation at room temperature and under atmospheric pressure. After 5 hours, the catalyst was filtered off and the filtrate was concentrated to about 50 ml. 200 ml of ethyl acetate was added and again the resultant solution was concentrated to about 60 ml so as to obtain the precipitate, which was allowed to stand overnight and filtered to obtain the titled compound.

Workup

  1. additionwas added
  2. temperaturewhile maintaining the temperature at -8° to -6° C
  3. customThe reaction liquid
  4. customto room temperature
  5. customover 2 hours
  6. stirringstirred at room temperature overnight
  7. filtrationThen, dicyclohexylurea was filtered off
  8. distillationdimethylformamide was distilled off under reduced pressure
  9. customThe residue was purified through the chromatography on silica gel (silica gel 1 kg
  10. customchloroform-methanol (3%→6%) as the eluent) and recrystallized from methanol-ethyl acetate

Sources & evidence

ORD record
ord-da0ee8d00c4c477189eb1502efc61dbd
Source dataset
uspto-grants-1989_11
Patent number
US04880819

Reaction notes

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