1-(2-(Dimethylamino)ethyl)piperazine → N-[4-({2-[({4-[2-(Dimethylamino)ethyl]piperazin-1-yl}carbonyl)amino]pyridin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 2066227ノート

反応式

HRID 2066227 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:47])[NH:39][C:40]5[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=5)[CH2:37][CH2:36]4)=[O:34])=[CH:28][CH:27]=3)[CH:22]=[CH:21][N:20]=2)C(OC2C=CC=CC=2)=O)C=CC=CC=1.[CH3:49][N:50]([CH3:59])[CH2:51][CH2:52][N:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1>CN(C)C=O>[CH3:49][N:50]([CH3:59])[CH2:51][CH2:52][N:53]1[CH2:58][CH2:57][N:56]([C:8]([NH:9][C:19]2[CH:24]=[C:23]([O:25][C:26]3[CH:27]=[CH:28][C:29]([NH:32][C:33]([C:35]4([C:38]([NH:39][C:40]5[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=5)=[O:47])[CH2:37][CH2:36]4)=[O:34])=[CH:30][CH:31]=3)[CH:22]=[CH:21][N:20]=2)=[O:7])[CH2:55][CH2:54]1

参加物

4

反応物 2

HCID 27362291-(2-(Dimethylamino)ethyl)piperazineHCID 59596935phenyl N-[4-(4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate

生成物 1

HCID 59597017N-[4-({2-[({4-[2-(Dimethylamino)ethyl]piperazin-1-yl}carbonyl)amino]pyridin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide収率 76.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To [4-(4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (50 mg) was added a solution of 1-[2-(dimethylamino)ethyl]piperazine (48.6 mg) in N,N-dimethylformamide (1.0 ml) at room temperature, followed by stirring for 5 hr. 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=95:5). Fractions containing the target compound were concentrated under reduced pressure. A solid was precipitated by addition of diethyl ether:heptane=1:3 to the resultant residue. The solvent was removed under reduced pressure. The solid residue was dried under reduced pressure to provide the titled compound as white powder (34.7 mg, 76%).

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. customThe solvent was removed under reduced pressure
  10. customThe solid residue was dried under reduced pressure

出典と根拠

ORDレコード
ord-286186c8ec894f908305c8b451060edc
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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