4-(Azetidin-1-ylmethyl)piperidine dihydrochloride → N-(4-{[2-({[4-(Azetidin-1-ylmethyl)piperidin-1-yl]carbonyl}amino)pyridin-4-yl]oxy}-2-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 2066234Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2066234
[F:1][C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][C:33]=1[NH:34][C:35]([C:37]1([C:40](=[O:49])[NH:41][C:42]2[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=2)[CH2:39][CH2:38]1)=[O:36])[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([N:12](C(OC2C=CC=CC=2)=O)[C:13](=O)[O:14]C2C=CC=CC=2)[CH:7]=1.Cl.Cl.[N:52]1([CH2:56][CH:57]2[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]2)[CH2:55][CH2:54][CH2:53]1>CN(C)C=O>[N:52]1([CH2:56][CH:57]2[CH2:62][CH2:61][N:60]([C:13]([NH:12][C:8]3[CH:7]=[C:6]([O:5][C:4]4[CH:31]=[CH:32][C:33]([NH:34][C:35]([C:37]5([C:40]([NH:41][C:42]6[CH:43]=[CH:44][C:45]([F:48])=[CH:46][CH:47]=6)=[O:49])[CH2:39][CH2:38]5)=[O:36])=[C:2]([F:1])[CH:3]=4)[CH:11]=[CH:10][N:9]=3)=[O:14])[CH2:59][CH2:58]2)[CH2:55][CH2:54][CH2:53]1

Komponenten

4

Edukt 2

HCID 231533864-(Azetidin-1-ylmethyl)piperidine dihydrochlorideHCID 59597026[4-(3-fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester

Produkt 1

HCID 16118533N-(4-{[2-({[4-(Azetidin-1-ylmethyl)piperidin-1-yl]carbonyl}amino)pyridin-4-yl]oxy}-2-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideAusbeute 48,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of phenyl N-[4-(3-fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate (50.0 mg) in N,N-dimethylformamide (2.0 ml) was added 4-(azetidin-1-ylmethyl)piperidine dihydrochloride (85.2 mg), followed by stirring at room temperature for 16 hr. The reaction mixture was partitioned between ethyl acetate and a 1N aqueous solution of sodium hydroxide. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed, and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate, then ethyl acetate:methanol=20:1). Fractions containing the target compound were concentrated. To the residue was added diethyl ether:hexane=1:3, and the precipitate was collected by filtration. This was washed with hexane and dried under aeration to provide the titled compound as white powder (21.9 mg, 48.3%).

Aufarbeitung

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed
  5. customthe residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate
  6. additionFractions containing the target compound
  7. concentrationwere concentrated
  8. additionTo the residue was added diethyl ether
  9. filtrationhexane=1:3, and the precipitate was collected by filtration
  10. washThis was washed with hexane
  11. customdried under aeration

Quellen und Nachweise

ORD-Eintrag
ord-99058cbdd6cd42588c55be995ee9d251
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08288538B2

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