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 2265674ノート

反応式

HRID 2265674 の反応式
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]

参加物

4

反応物 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

生成物 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-dicarboxamide収率 14%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-f5bb095d6f0946019006dece8db72c3c
出典データセット
uspto-grants-2010_12
特許番号
US07855290B2

反応ノート

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