Triethylamine → 6-Fluoro-1-(2,4-difluorophenyl)-1,4-dihydro7-(5-methyl-2,5-diazabicyclo(2.2.1)hept-2-yl)-4-oxoquinoline-3-carboxylic acid

HRID 727937

Reaktionsgleichung

Reaktionsgleichung von HRID 727937
Cl[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:23])[C:7]([C:20]([OH:22])=[O:21])=[CH:8][N:9]2[C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=2[F:19])=[CH:4][C:3]=1[F:24].FOBOF.[CH3:30][N:31]1[CH2:36][CH:35]2[CH2:37][CH:32]1[CH2:33][NH:34]2.C(N(CC)CC)C>FB(O)O.CS(C)=O.O>[F:24][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[N:34]1[CH2:33][CH:32]3[CH2:37][CH:35]1[CH2:36][N:31]3[CH3:30])[N:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[F:19])[CH:8]=[C:7]([C:20]([OH:22])=[O:21])[C:6]2=[O:23]

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 102194032-Methyl-2,5-diazabicyclo[2.2.1]heptaneHCID 11484989HCID 11484989, VerbindungHCID 178506430HCID 178506430, Verbindung

Produkt 1

HCID 140148276-Fluoro-1-(2,4-difluorophenyl)-1,4-dihydro7-(5-methyl-2,5-diazabicyclo(2.2.1)hept-2-yl)-4-oxoquinoline-3-carboxylic acidAusbeute 18,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 679Dimethyl SulfoxideLösungsmittelHCID 962WaterLösungsmittelHCID 14595563Fluoroboronic acidLösungsmittel

Versuchsvorschrift

15 g (37.36 m Mol) of the mixed anhydride of 7-chloro-6-fluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid and difluoroboronic acid (obtained by heating 7-chloro-6-fluoro-1-(2.4-difluoro- phenyl)-1,4-dihycho-4-oxoquinoline-3-carboxylic acid in 60% aqueous fluoroboronic acid 15.36 g (56 m Mol) of the dihydrobromide of 2-methyl-2,5-diazabicyclo-(2.2.1)heptane and 31 ml (0.224 mol) triethylamine was stirred in 200 ml of dry DMSO at room temperature for 6 days. Then the reaction mixture was poured into 800 ml of cold water and the resultant precipitate collected by filtration washed with water and then heated to reflux with stirring in a mixture of 100 ml dioxane and 150 ml 3N NaOH for 1 hr. After cooling and with stirring, 500 ml of conc. HCl was added. After stirring for 1 hr., the undissolved material was removed by filtration, to give a clear solution which was extracted multiple times with methylene chloride. The aqueous phase was cooled in an ice bath and brought to pH 7.4 by the addition of dilute NaOH. The resultant was extracted with chloroform and the chloroform phase dried over sodium sulfate and the chloroform removed in vacuo, the resulting dark brown oil was recrystallized from 450 ml ethanol to give 3.15 g (18.8%) of the product as a hydrate, mp 215° C.-220° C. dec.

Aufarbeitung

  1. filtrationthe resultant precipitate collected by filtration
  2. washwashed with water
  3. temperatureheated
  4. temperatureto reflux
  5. temperatureAfter cooling
  6. stirringwith stirring
  7. addition500 ml of conc. HCl was added
  8. stirringAfter stirring for 1 hr
  9. custom, the undissolved material was removed by filtration
  10. customto give a clear solution which
  11. extractionwas extracted multiple times with methylene chloride
  12. temperatureThe aqueous phase was cooled in an ice bath
  13. additionbrought to pH 7.4 by the addition of dilute NaOH
  14. extractionThe resultant was extracted with chloroform
  15. dry with materialthe chloroform phase dried over sodium sulfate
  16. customthe chloroform removed in vacuo
  17. customthe resulting dark brown oil was recrystallized from 450 ml ethanol

Quellen und Nachweise

ORD-Eintrag
ord-05d7c736c7aa49b794b4ae455df8a8fd
Quelldatensatz
uspto-grants-1991_09
Patentnummer
US05045549

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