Diethyl Ether → 6-methoxy-1,5-naphthyridin-4-ol

HRID 1271677Notes

Reaction equation

HRID 1271677 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[C:10](OC)(=[O:13])[C:11]#[CH:12].CCOCC>CO.C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1>[CH3:9][O:8][C:5]1[N:6]=[C:7]2[C:2](=[CH:3][CH:4]=1)[NH:1][CH:12]=[CH:11][C:10]2=[O:13]

Participants

6

Reactant 3

HCID 3283Diethyl EtherHCID 13536Methyl propiolateHCID 811216-Methoxy-3-pyridinylamine

Product 1

HCID 113788076-methoxy-1,5-naphthyridin-4-olYield 70%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 246701,1'-Biphenyl, mixt. with 1,1'-oxybis(benzene)Solvent2×

Procedure

5-Amino-2-methoxypyridine (55 g, 0.44 mol) in methanol (1000 ml) with methyl propiolate (40 ml, 0.44 mol) was stirred for 48 hours, then evaporated and the product purified by chromatography on silica gel (dichloromethane) followed by recrystallisation from dichloromethane-hexane (44.6 g, 48%). The unsaturated ester (10.5 g, 0.05 mol) in warm Dowtherm A (50 ml) was added over 3 minutes to refluxing Dowtherm A, and after a further 20 minutes at reflux the mixture was cooled and poured into ether. The precipate was filtered to give a white solid (6.26 g, 70%).

Workup

  1. customevaporated
  2. customthe product purified by chromatography on silica gel (dichloromethane)
  3. customfollowed by recrystallisation from dichloromethane-hexane (44.6 g, 48%)
  4. temperatureafter a further 20 minutes at reflux the mixture
  5. temperaturewas cooled
  6. filtrationThe precipate was filtered

Sources & evidence

ORD record
ord-3a8cfa113d31424082fba6eedaa5d3e3
Source dataset
uspto-grants-2007_04
Patent number
US07205408B2

Reaction notes

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