Ammonia → Vatalanib

HRID 649787

Reaktionsgleichung

Reaktionsgleichung von HRID 649787
O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.Cl.C(N(CC)CC)C.[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[CH:26][CH:25]=1.[N:31]1[CH:36]=[CH:35][C:34]([CH2:37][C:38]2[C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[C:41](=O)[NH:40][N:39]=2)=[CH:33][CH:32]=1.N>C(Cl)(Cl)Cl.O>[Cl:23][C:24]1[CH:30]=[CH:29][C:27]([NH:28][C:41]2[C:42]3[C:47](=[CH:46][CH:45]=[CH:44][CH:43]=3)[C:38]([CH2:37][C:34]3[CH:35]=[CH:36][N:31]=[CH:32][CH:33]=3)=[N:39][N:40]=2)=[CH:26][CH:25]=1

Komponenten

8

Edukt 5

HCID 222AmmoniaHCID 78124-ChloroanilineHCID 11130Triethylamine hydrochlorideHCID 14812Phosphorus oxide (P4O10)HCID 7899544-(4-Pyridylmethyl)-1(2H)-phtalazinone

Produkt 1

HCID 151194Vatalanib

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6212ChloroformLösungsmittel

Reaktionsbedingungen

Temperatur
200 °C

Versuchsvorschrift

A mixture of 14.19 g (0.1 mol) phosphorus pentoxide, 13.77 g (0.1 mol) triethylamine hydrochloride and 12.76 g (0.1 mol) 4-chloroaniline is heated and stirred in a nitrogen atmosphere at 200° C. until a homogeneous melt has formed (about 20 min). To the melt, 5.93 g (0.025 mol) 4-(4-pyridylmethyl)-1(2H)-phthalazinone (for preparation see German Auslegeschrift no. 1 061 788 [published 23.07.1959]) is added, and the reaction mixture is stirred for 3 h at 200° C. After the reaction mixture has cooled to about 100° C., 200 ml of water is added. Stirring is continued until the temperature reaches about 30° C., and then 20 ml conc. ammonia (30% aqueous ammonium hydroxide solution) and 900 ml chloroform are added consecutively. As soon as a diphasic mixture has formed, the organic phase is separated off, dried over anhydrous sodium sulfate, filtered, and the filtrate evaporated on a RE to a volume of about 50 ml, to which 100 ml acetate is then added, and the mixture is cooled in an ice bath. The crystallizate obtained is filtered off and washed with acetate and ether. After recrystallization from methanol and drying under HV for 8 h at 120° C., the title compound is obtained; m.p. 194-195° C.; ESI-MS: (M+H)+=347.

Aufarbeitung

  1. temperatureis heated
  2. customhas formed (about 20 min)
  3. stirringthe reaction mixture is stirred for 3 h at 200° C
  4. temperatureAfter the reaction mixture has cooled to about 100° C.
  5. stirringStirring
  6. customreaches about 30° C.
  7. customAs soon as a diphasic mixture has formed
  8. customthe organic phase is separated off
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. customthe filtrate evaporated on a RE to a volume of about 50 ml
  12. additionto which 100 ml acetate is then added
  13. temperaturethe mixture is cooled in an ice bath
  14. customThe crystallizate obtained
  15. filtrationis filtered off
  16. washwashed with acetate and ether
  17. customAfter recrystallization from methanol
  18. customdrying under HV for 8 h at 120° C.

Quellen und Nachweise

ORD-Eintrag
ord-e90e1a5501af4bc5bc05c3da50001359
Quelldatensatz
uspto-grants-2001_08
Patentnummer
US06271233B1

Verknüpfte Notizen

Wird geladen…