1-Methyl-4-(methylamino)piperidine → N-(2,4-Difluorophenyl)-N'-(2-fluoro-4-{[2-({[methyl(1-methylpiperidin-4-yl)amino]carbonyl}amino)pyridin-4-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide

HRID 2066244Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2066244
C1([O:7][C:8](=O)[N:9]([C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33]([C:35]4([C:38](=[O:48])[NH:39][C:40]5[CH:45]=[CH:44][C:43]([F:46])=[CH:42][C:41]=5[F:47])[CH2:37][CH2:36]4)=[O:34])=[C:28]([F:49])[CH:27]=3)[CH:22]=[CH:21][N:20]=2)C(OC2C=CC=CC=2)=O)C=CC=CC=1.[CH3:51][N:52]1[CH2:57][CH2:56][CH:55]([NH:58][CH3:59])[CH2:54][CH2:53]1>CN(C)C=O>[F:47][C:41]1[CH:42]=[C:43]([F:46])[CH:44]=[CH:45][C:40]=1[NH:39][C:38]([C:35]1([C:33]([NH:32][C:29]2[CH:30]=[CH:31][C:26]([O:25][C:23]3[CH:22]=[CH:21][N:20]=[C:19]([NH:9][C:8]([N:58]([CH3:59])[CH:55]4[CH2:56][CH2:57][N:52]([CH3:51])[CH2:53][CH2:54]4)=[O:7])[CH:24]=3)=[CH:27][C:28]=2[F:49])=[O:34])[CH2:37][CH2:36]1)=[O:48]

Komponenten

4

Edukt 2

HCID 5663231-Methyl-4-(methylamino)piperidineHCID 59596952[4-(4-{[1-(2,4-Difluorophenylcarbamoyl)cyclopropanecarbonyl]amino}-3-fluorophenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester

Produkt 1

HCID 59596895N-(2,4-Difluorophenyl)-N'-(2-fluoro-4-{[2-({[methyl(1-methylpiperidin-4-yl)amino]carbonyl}amino)pyridin-4-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamideAusbeute 14 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of [4-(4-{[1-(2,4-Difluorophenylcarbamoyl)cyclopropanecarbonyl]amino}-3-fluorophenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (116 mg) in N,N-dimethylformamide (2.0 ml) was added 1-methyl-4-(methylamino)piperidine (0.150 ml) at room temperature, followed by stirring overnight. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with a saturated aqueous solution of ammonium chloride and brine in this order, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=98:2). Fractions containing the target compound were concentrated under reduced pressure. A solid was precipitated by addition of diethyl ether:heptane=1:1 to the resultant residue. The solid was collected by filtration. The solid was dried under aeration to provide the titled compound as white powder (14.0 mg, 14%).

Aufarbeitung

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. washThe organic layer was washed with a saturated aqueous solution of ammonium chloride and brine in this order
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationThe solvent was concentrated under reduced pressure
  5. customThe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent
  6. additionFractions containing the target compound
  7. concentrationwere concentrated under reduced pressure
  8. customA solid was precipitated by addition of diethyl ether
  9. filtrationThe solid was collected by filtration
  10. customThe solid was dried under aeration

Quellen und Nachweise

ORD-Eintrag
ord-552e41ce39434eea818346b25c5fd335
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08288538B2

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