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

HRID 2066210ノート

反応式

HRID 2066210 の反応式
C1(OC(=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:10]([O:12]C2C=CC=CC=2)=O)C=CC=CC=1.[CH3:49][NH:50][CH:51]1[CH2:56][CH2:55][N:54]([CH3:57])[CH2:53][CH2:52]1>CN(C)C=O>[F:46][C:43]1[CH:42]=[CH:41][C:40]([NH:39][C:38]([C:35]2([C:33]([NH:32][C:29]3[CH:30]=[CH:31][C:26]([O:25][C:23]4[CH:22]=[CH:21][N:20]=[C:19]([NH:9][C:10]([N:50]([CH3:49])[CH:51]5[CH2:56][CH2:55][N:54]([CH3:57])[CH2:53][CH2:52]5)=[O:12])[CH:24]=4)=[CH:27][CH:28]=3)=[O:34])[CH2:36][CH2:37]2)=[O:47])=[CH:45][CH:44]=1

参加物

4

反応物 2

HCID 5663231-Methyl-4-(methylamino)piperidineHCID 59596935phenyl N-[4-(4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate

生成物 1

HCID 59596924N-(4-Fluorophenyl)-N'-(4-{[2-({[methyl(1-methylpiperidin-4-yl)amino]carbonyl}amino)pyridin-4-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide収率 86.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

[4-(4-{[1-(4-Fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (50 mg) was dissolved in N,N-dimethylformamide (1.0 ml), and methyl(1-methylpiperidin-4-yl)amine (0.045 ml) was added thereto, followed by stirring for 62 hr. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of sodium hydrogencarbonate (20 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml) in this order, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and 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, and the resultant residue was suspended in diethyl ether (2 ml) and hexane (4 ml). The solid was collected by filtration and dried under aeration to provide the titled compound as white powder (37.6 mg, 86.8%).

後処理

  1. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
  2. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (20 ml), water (20 ml) and brine (20 ml) in this order
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed 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. filtrationThe solid was collected by filtration
  9. customdried under aeration

出典と根拠

ORDレコード
ord-8c124843ab5f46c599f0e96a8bf54cc6
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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