Hydrochloric Acid → 3-[3-Ethoxy-6-ethoxycarbonyl-5-(4-methoxyanilino)-1,8-naphthyridin-2-yl]acrylic acid hemihydrochloride

HRID 128628Notes

Reaction equation

HRID 128628 reaction equation
[ClH:1].[CH2:2]([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[N:13][C:14]=1[CH3:15])[N:11]=[CH:10][C:9]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:8]2[NH:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=1)[CH3:3].[C:30]([OH:34])(=[O:33])[CH:31]=O.C(=O)(O)[O-].[Na+].Cl>O.C(O)(=O)C>[ClH:1].[CH2:2]([O:4][C:5]1[C:14]([CH:15]=[CH:31][C:30]([OH:34])=[O:33])=[N:13][C:12]2[C:7]([CH:6]=1)=[C:8]([NH:21][C:22]1[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=1)[C:9]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:10][N:11]=2)[CH3:3].[CH2:2]([O:4][C:5]1[C:14]([CH:15]=[CH:31][C:30]([OH:34])=[O:33])=[N:13][C:12]2[C:7]([CH:6]=1)=[C:8]([NH:21][C:22]1[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=1)[C:9]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:10][N:11]=2)[CH3:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 760Glyoxylic AcidHCID 516892Sodium BicarbonateHCID 19374282Ethyl 4-(4-methoxyanilino)-6-ethoxy-7-methyl-1,8-naphthyridine-3-carboxylate hydrochloride

Product 1

HCID 1317191773-[3-Ethoxy-6-ethoxycarbonyl-5-(4-methoxyanilino)-1,8-naphthyridin-2-yl]acrylic acid hemihydrochloride

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

A mixture of ethyl 6-ethoxy-4-(4-methoxyanilino)-7-methyl-1,8-naphthyridine-3-carboxylate hydrochloride (4.76 g), glyoxylic acid (1.73 g) and glacial acetic acid (50 ml) was boiled under reflux for 24 hours. The mixture was cooled and a solid was collected by filtration. The filtrate was acidified with concentrated hydrochloric acid and filtered to give a second crop of solid. The two crops of solid were combined, stirred in water and the mixture basified with sodium bicarbonate. The pH of the mixture was adjusted to pH 6 with concentrated hydrochloric acid and the mixture was extracted with ethyl acetate and then with dichloromethane. The combined organic extracts were washed with water, dried and evaporated. The residue was triturated with ethyl acetate and then filtered to give 3-[3-ethoxy-6-ethoxycarbonyl-5-(4-methoxyanilino)-1,8-naphthyridin-2-yl]acrylic acid hemihydrochloride, m.p. 259°-261° C.

Workup

  1. temperatureunder reflux for 24 hours
  2. temperatureThe mixture was cooled
  3. filtrationa solid was collected by filtration
  4. filtrationfiltered
  5. customto give a second crop of solid
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe combined organic extracts were washed with water
  8. customdried
  9. customevaporated
  10. customThe residue was triturated with ethyl acetate
  11. filtrationfiltered

Sources & evidence

ORD record
ord-07efd22cd5d24ce2b55488eaf85c7440
Source dataset
uspto-grants-1995_11
Patent number
US05464781

Reaction notes

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