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 2066234ノート

反応式

HRID 2066234 の反応式
[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

参加物

4

反応物 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

生成物 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-dicarboxamide収率 48.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-99058cbdd6cd42588c55be995ee9d251
出典データセット
uspto-grants-2012_10
特許番号
US08288538B2

反応ノート

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