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Cesium carbonate → N-(4-(7-(3-(7-hydroxy-5-azaspiro[2.4]heptane-5-yl)propoxy)-6-methoxyquinolin-4-yloxy)-3-fluorophenyl)-N-phenylcyclopropane-1,1-dicarboxamide

HRID 2068212
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HRID 2068212 반응식
[F:1][C:2]1[CH:3]=[C:4]([N:22]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:23]([C:25]2([C:28]([NH2:30])=[O:29])[CH2:27][CH2:26]2)=[O:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([OH:21])=[C:16]([O:19][CH3:20])[CH:17]=2)[N:12]=[CH:11][CH:10]=1.CS(O[CH2:42][CH2:43][CH2:44][N:45]1[CH2:51][CH:50]([OH:52])[C:47]2([CH2:49][CH2:48]2)[CH2:46]1)(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CC(N(C)C)=O>[OH:52][CH:50]1[C:47]2([CH2:49][CH2:48]2)[CH2:46][N:45]([CH2:44][CH2:43][CH2:42][O:21][C:15]2[CH:14]=[C:13]3[C:18]([C:9]([O:8][C:7]4[CH:6]=[CH:5][C:4]([N:22]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)[C:23]([C:25]5([C:28]([NH2:30])=[O:29])[CH2:27][CH2:26]5)=[O:24])=[CH:3][C:2]=4[F:1])=[CH:10][CH:11]=[N:12]3)=[CH:17][C:16]=2[O:19][CH3:20])[CH2:51]1
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참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 86640798HCID 86640798, 화합물HCID 136381441N-(3-fluoro-4-(7-hydroxy-6-methoxyquinolin-4-yloxy)phenyl)-N-phenylcyclopropane-1,1-dicarboxamide

생성물 1

HCID 68636350N-(4-(7-(3-(7-hydroxy-5-azaspiro[2.4]heptane-5-yl)propoxy)-6-methoxyquinolin-4-yloxy)-3-fluorophenyl)-N-phenylcyclopropane-1,1-dicarboxamide수율 77.2%

시약·촉매·용매 1

HCID 31374
Dimethylacetamide
용매

실험 절차

To a solution of N-(3-fluoro-4-(7-hydroxy-6-methoxyquinolin-4-yloxy)phenyl)-N-phenylcyclopropane-1,1-dicarboxamide (260 mg, 0.534 mmol) in DMA (3 mL) was added 3-(7-hydroxy-5-azaspiro[2.4]heptane-5-yl)propyl methanesulfonate (266 mg, 1.068 mmol) and Cs2CO3 (520 mg, 1.602 mmol). The reaction was then stirred at rt for 2 days. The solvent was removed and the residue was partioned between saturated NaHCO3 aqueous solution (15 mL) and CHCl3 (30 mL). The organic layer was dried over anhydrous Na2SO4, filtered and the filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (100:15:1(v/v/v)EtOAc/CH3OH/Et3N) to afford the desired compound as a pale yellow solid (264 mg, 77%).

후처리

  1. customThe solvent was removed
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe residue was purified by a silica gel column chromatography (100:15:1(v/v/v)EtOAc/CH3OH/Et3N)

출처 및 근거

ORD 기록
ord-827bc6733e694def975fbd7e0d4e5244
출처 데이터셋
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08293897B2

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