Sodium Chloride → 4Diethylamino-but-2-enoic acid [4(3-bromo-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amide

HRID 612135Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 612135
[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([NH2:20])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:23]#[N:24])[CH:5]=[CH:6][C:7]=1[F:8].[CH3:25][CH2:26][N:27]([CH:31]([CH3:33])C)[CH:28]([CH3:30])C.BrC/C=[CH:37]/[C:38](Cl)=[O:39].[Na+].[Cl-].C(NCC)C.C(=O)(O)[O-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:21][CH3:22])=[C:17]([NH:20][C:38](=[O:39])[CH:37]=[CH:33][CH2:31][N:27]([CH2:26][CH3:25])[CH2:28][CH3:30])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:23]#[N:24])[CH:5]=[CH:6][C:7]=1[F:8]

Komponenten

8

Edukt 6

HCID 5234Sodium ChlorideHCID 8021DiethylamineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 11263885(E)-4-Bromo-2-butenoyl ChlorideHCID 224666136-Amino-4-[(3-bromo-4-fluorophenyl)amino]-7-methoxy-3-quinolinecarbonitrile

Produkt 1

HCID 544873344Diethylamino-but-2-enoic acid [4(3-bromo-4-fluoro-phenylamino)-3-cyano-7-methoxy-quinolin-6-yl]-amideAusbeute 38,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

To a mixture of 0.77 g (1.98 mmol) of 4-[(3-bromo-4-fluorophenyl)amino]-7-methoxy-6-amino-quinoline-3-carbonitrile and 3.5 ml (20 mmol) of Hunig's base in 35 ml of dry THF at 0° C., with stirring, was added a THF solution containing 2.2 g (12 mmol) of 4-bromo crotonyl chloride dropwise. The mixture was stirred for additional 30 minutes at 0° C. 50 ml of saturated NaCl solution was added to the reaction mixture, then it was extracted with ethyl acetate. The ethyl acetate solution was dried over sodium sulfate and then was added to a solution of 3.1 ml (30 mmol) of diethyl amine in 5 ml of THF at 0° C. dropwise. The solution was stirred an additional hour at 0° C. and 30 minutes at room temperature. The mixture was poured into diluted sodium bicarbonate solution. The organic layer was dried over sodium sulfate and solvent was removed under vacuum. The residue was chromatographed to give 0.4 g off-white solid: mass spectrum (electrospray, m/e): M+H 525.9 and 527.9.

Aufarbeitung

  1. stirringThe mixture was stirred for additional 30 minutes at 0° C
  2. extractionit was extracted with ethyl acetate
  3. dry with materialThe ethyl acetate solution was dried over sodium sulfate
  4. stirringThe solution was stirred an additional hour at 0° C. and 30 minutes at room temperature
  5. dry with materialThe organic layer was dried over sodium sulfate and solvent
  6. customwas removed under vacuum
  7. customThe residue was chromatographed

Quellen und Nachweise

ORD-Eintrag
ord-e5aa12e2149946378af5e54c9e819eef
Quelldatensatz
uspto-grants-1999_12
Patentnummer
US06002008

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