1-Chloro-4-isocyanato-2-(trifluoromethyl) benzene → Regorafenib

HRID 475440Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 475440
[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[C:14]([F:19])[CH:13]=2)[CH:8]=[CH:7][N:6]=1)=[O:4].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]=[C:28]=[O:29])=[CH:23][C:22]=1[C:30]([F:33])([F:32])[F:31]>C1(C)C=CC=CC=1>[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[C:9]([O:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:28]([NH:27][C:24]3[CH:25]=[CH:26][C:21]([Cl:20])=[C:22]([C:30]([F:32])([F:31])[F:33])[CH:23]=3)=[O:29])=[C:14]([F:19])[CH:13]=2)[CH:8]=[CH:7][N:6]=1)=[O:4]

Komponenten

4

Edukt 2

HCID 27332651-Chloro-4-isocyanato-2-(trifluoromethyl) benzeneHCID 468352194-(4-Amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide

Produkt 1

HCID 11167602RegorafenibAusbeute 47,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Versuchsvorschrift

To a solution of 4-(4-amino-3-fluorophenoxy)pyridine-2-carboxylic acid methylamide (177 mg, 0.68 mmol) in toluene (3 mL) was added 4-chloro-3-(trifluoromethyl)phenyl isocyanate (150 mg, 0.68 mmol). The mixture was stirred at rt for 72 h. The reaction was concentrated under reduced pressure and the residue was triturated with diethylether. The resulting solid was collected by filtration and dried in vacuo for 4 h to afford the title compound (155 mg, 0.32 mmol; 47% yield); 1H-NMR (DMSO-d6) 2.78 (d, J=4.9, 3H), 7.03-7.08 (m, 1H), 7.16 (dd, J=2.6, 5.6, 1H), 7.32 (dd, J=2.7, 11.6, 1H), 7.39 (d, J=2.5, 1H), 7.60 (s, 2H), 8.07-8.18 (m, 2H), 8.50 (d, J=5.7, 1H), 8.72 (s, 1H), 8.74-8.80 (m, 1H), 9.50 (s, 1H); MS (HPLC/ES) 483.06 m/z=(M+1).

Aufarbeitung

  1. concentrationThe reaction was concentrated under reduced pressure
  2. customthe residue was triturated with diethylether
  3. filtrationThe resulting solid was collected by filtration
  4. customdried in vacuo for 4 h

Quellen und Nachweise

ORD-Eintrag
ord-a0df1dc4c8a148b386b384380c4fcb5a
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08637553B2

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