Ammonia → Vatalanib

HRID 49860

反応式

HRID 49860 の反応式
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

参加物

8

反応物 5

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

生成物 1

HCID 151194Vatalanib

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6212Chloroform溶媒

反応条件

温度
200 °C

実験手順

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. 1061 788 [published Jul. 23, 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.

後処理

  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.

出典と根拠

ORDレコード
ord-0bea44cdb2d342e2a51397ee5ab17535
出典データセット
uspto-grants-2004_03
特許番号
US06710047B2

関連ノート

読み込み中…