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Triethylamine → N-{4-[(2-{[(4-Azetidin-1-ylpiperidin-1-yl)carbonyl]amino}pyridin-4-yl)oxy]-3-fluorophenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 2066209
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HRID 2066209 반응식
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][C:27]=3[F:48])[CH:22]=[CH:21][N:20]=2)C(OC2C=CC=CC=2)=O)C=CC=CC=1.Cl.Cl.[N:52]1([CH:56]2[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]2)[CH2:55][CH2:54][CH2:53]1.C(N(CC)CC)C>CN(C)C=O>[N:52]1([CH:56]2[CH2:61][CH2:60][N:59]([C:8]([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][C:27]=4[F:48])[CH:22]=[CH:21][N:20]=3)=[O:7])[CH2:58][CH2:57]2)[CH2:55][CH2:54][CH2:53]1
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참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 231531084-(Azetidin-1-yl)piperidine dihydrochlorideHCID 59597000[4-(2-Fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester

생성물 1

HCID 59596993N-{4-[(2-{[(4-Azetidin-1-ylpiperidin-1-yl)carbonyl]amino}pyridin-4-yl)oxy]-3-fluorophenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide수율 59%

시약·촉매·용매

1
HCID 6228Dimethylformamide용매

실험 절차

To a solution of [4-(2-fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-(phenoxycarbonyl)carbamic acid phenyl ester (66 mg) in N,N-dimethylformamide (1.0 ml) were added 4-(azetidin-1-yl)piperidine dihydrochloride (85 mg) and triethylamine (0.112 ml) at room temperature, followed by stirring for 24 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 solid was collected by filtration and dried under aeration to provide the titled compound as white powder (34.6 mg, 59%).

후처리

  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. customdried under aeration

출처 및 근거

ORD 기록
ord-96917c432e1d448bb1384b449ca83141
출처 데이터셋
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08288538B2

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