Hydrochloric Acid → HCID 67626402, compound

HRID 128627Notes

Reaction equation

HRID 128627 reaction equation
[ClH:1].[CH2:2]([O:4][C:5]1[C:6]([CH3:24])=[N:7][C:8]2[C:13]([CH:14]=1)=[C:12]([NH:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)[CH:11]=[CH:10][N:9]=2)[CH3:3].O.[C:26]([OH:30])(=[O:29])[CH:27]=[O:28].FC(F)(F)C(O)=O.Cl>C(=O)(O)[O-].[Na+].O.C(O)(=O)C>[OH2:4].[OH2:28].[ClH:1].[CH2:2]([O:4][C:5]1[C:6]([CH:24]=[CH:27][C:26]([OH:30])=[O:29])=[N:7][C:8]2[C:13]([CH:14]=1)=[C:12]([NH:15][C:16]1[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=1)[CH:11]=[CH:10][N:9]=2)[CH3:3]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 15620607Glyoxylic acid, monohydrateHCID 19374274HCID 19374274, compound

Product 1

HCID 67626402HCID 67626402, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 3-ethoxy-5-(4-methoxyanilino)-2-methyl-1,8-naphthyridine hydrochloride (5.0 g), glyoxylic acid monohydrate (2.2 g) and glacial acetic acid (50 ml) were stirred and treated dropwise with trifluoroacetic acid (12.5 ml). The mixture was stirred and heated at 95° C. for 22 hours and cooled to ambient temperature. The mixture was filtered and the solid obtained was stirred in sodium bicarbonate solution (100 ml) for 15 minutes. The mixture was filtered. The solid obtained was stirred in water (100 ml) and acidified with concentrated hydrochloric acid to pH 1. After stirring for an hour the mixture was filtered to give a solid. The filtrate was evaporated to dryness and the residue triturated with water and filtered. The crops of solid were combined, dissolved in dichloromethane/methanol, dried, filtered and evaporated. The residue was triturated with hot ethyl acetate and hot filtered. The solid obtained was combined with the solid obtained from the acidic mixture above, triturated with hot ethyl acetate and hot filtered. The solid obtained was purified by flash column chromatography on silica using a mixture of ethyl acetate:dichloromethane:methanol, 5:5:1 and then 1:1:1 to give a solid. The solid was triturated with hot ethyl acetate and hot filtered to give 3-[3-ethoxy-5-(4-methoxyanilino)-1,8-naphthyridin-2-yl]acrylic acid hydrochloride dihydrate, m.p. 230°-235° C. (with decomposition).

Workup

  1. stirringThe mixture was stirred
  2. temperaturecooled to ambient temperature
  3. filtrationThe mixture was filtered
  4. customthe solid obtained
  5. filtrationThe mixture was filtered
  6. customThe solid obtained
  7. stirringAfter stirring for an hour the mixture
  8. filtrationwas filtered
  9. customto give a solid
  10. customThe filtrate was evaporated to dryness
  11. customthe residue triturated with water
  12. filtrationfiltered
  13. dissolutiondissolved in dichloromethane/methanol
  14. customdried
  15. filtrationfiltered
  16. customevaporated
  17. customThe residue was triturated with hot ethyl acetate and hot filtered
  18. customThe solid obtained
  19. customobtained from the acidic mixture above,
  20. customtriturated with hot ethyl acetate and hot filtered
  21. customThe solid obtained
  22. customwas purified by flash column chromatography on silica using
  23. additiona mixture of ethyl acetate
  24. customdichloromethane:methanol, 5:5:1 and then 1:1:1 to give a solid
  25. customThe solid was triturated with hot ethyl acetate
  26. filtrationhot filtered

Sources & evidence

ORD record
ord-26fa810e1cfc4b61808eaa85bf985e30
Source dataset
uspto-grants-1995_11
Patent number
US05464781

Reaction notes

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