Triethylamine → 4-Methyl-N-[2-(6-bromo-1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazinecarboxamide maleate

HRID 4099

Reaktionsgleichung

Reaktionsgleichung von HRID 4099
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:17]2[C:12](=[CH:13][C:14]([Br:18])=[CH:15][CH:16]=2)[CH2:11][CH2:10][CH2:9]1.C(N(CC)CC)C.C1(O[C:33](Cl)=[O:34])C=CC=CC=1.[CH3:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.[C:43]([OH:50])(=[O:49])/[CH:44]=[CH:45]\[C:46]([OH:48])=[O:47]>ClCCl.C(O)C.O>[C:43]([OH:50])(=[O:49])/[CH:44]=[CH:45]\[C:46]([OH:48])=[O:47].[CH3:36][N:37]1[CH2:42][CH2:41][N:40]([C:33]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[N:8]2[C:17]3[C:12](=[CH:13][C:14]([Br:18])=[CH:15][CH:16]=3)[CH2:11][CH2:10][CH2:9]2)=[O:34])[CH2:39][CH2:38]1

Komponenten

9

Edukt 5

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 531671-Methylpiperazine2×HCID 444266Maleic AcidHCID 138129321-(2-Aminophenyl)-6-bromo-1,2,3,4-tetrahydroquinoline

Produkt 1

HCID 704071784-Methyl-N-[2-(6-bromo-1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazinecarboxamide maleateAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

A stirred solution, under nitrogen, of 1-(2-aminophenyl)-6-bromo-1,2,3,4-tetrahydroquinoline (21.2 g, 0.070 mole) and triethylamine (10.1 g, 0.10 mole) in dichloromethane (200 ml) was cooled to 0° C. Then there was added dropwise phenylchloroformate (15.7 g, 0.10 mole) at such a rate as to keep the reaction temperature below 5° C. The addition took 30 minutes. The mixture was stirred for 1 hour at ice-bath temperature, 2 hours at room temperature, and N-methylpiperazine (28.1 g, 0.28 mole) dissolved in dichloromethane (30 ml) was added dropwise over a 45 minute period. The solution was stirred for 3 hours and an additional charge of N-methylpiperazine (14.05 g, 0.14 mole) dissolved in dichloromethane (15 ml) was added, and the mixture was stirred overnight. Water (250 ml) was added with vigorous stirring. The layers were separated and the organic phase was washed twice with water, dried over anhydrous sodium sulfate and concentrated. The residue was dissolved in ethanol (200 ml), with heating, and treated with a warm solution of maleic acid (8.93 g, 0.077 mole) in ethanol (100 ml). The maleate salt was collected to give 23.2 g (61%) of product. Recrystallization from methanol afforded the analytical sample, mp 172°-174° C.

Aufarbeitung

  1. customthe reaction temperature below 5° C
  2. additionThe addition
  3. additionwas added dropwise over a 45 minute period
  4. stirringThe solution was stirred for 3 hours
  5. additionwas added
  6. stirringthe mixture was stirred overnight
  7. customThe layers were separated
  8. washthe organic phase was washed twice with water
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. dissolutionThe residue was dissolved in ethanol (200 ml)
  12. temperaturewith heating
  13. customThe maleate salt was collected

Quellen und Nachweise

ORD-Eintrag
ord-c8d324b564d0491d91020d54c175f9db
Quelldatensatz
uspto-grants-1988_02
Patentnummer
US04723003

Verknüpfte Notizen

Wird geladen…