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

HRID 2066225ノート

反応式

HRID 2066225 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](OC2C=CC=CC=2)=[O:11])C=CC=CC=1.Cl.Cl.Cl.[N:52]1([CH2:56][CH2:57][N:58]2[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]2)[CH2:55][CH2:54][CH2:53]1.C(N(CC)CC)C.O>CN(C)C=O>[N:52]1([CH2:56][CH2:57][N:58]2[CH2:59][CH2:60][N:61]([C:10]([NH:9][C:19]3[CH:24]=[C:23]([O:25][C:26]4[CH:31]=[CH:30][C:29]([NH:32][C:33]([C:35]5([C:38]([NH:39][C:40]6[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=6)=[O:47])[CH2:37][CH2:36]5)=[O:34])=[CH:28][CH:27]=4)[CH:22]=[CH:21][N:20]=3)=[O:11])[CH2:62][CH2:63]2)[CH2:53][CH2:54][CH2:55]1

参加物

6

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 231529971-[2-(Azetidin-1-yl)ethyl]piperazine trihydrochlorideHCID 59596935phenyl N-[4-(4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate

生成物 1

HCID 59596958N-(4-{[2-({[4-(2-Azetidin-1-ylethyl)piperazin-1-yl]carbonyl}amino)pyridin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide収率 51.2%

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 1-[2-(azetidin-1-yl)ethyl]piperazine trihydrochloride (64.6 mg), triethylamine (0.129 ml) and water (0.100 ml) were added thereto in this order, followed by stirring for 20 hr. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of ammonium chloride (20 ml). The organic layer was washed with a saturated aqueous solution of ammonium chloride (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=9:1). 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 (23.8 mg, 51.2%).

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 ammonium chloride (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-8e1df6cdfa6c436d862c3cbaf51055c0
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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