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1,2-Dichloroethane → N'-(4-(2-(2,2-Dimethylhydrazinecarbonyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamide

HRID 418675
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HRID 418675 반응식
N[C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]([NH:18][N:19]([CH3:21])[CH3:20])=[O:17])[S:15][C:8]=23)=[C:4]([F:24])[CH:3]=1.[CH3:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[NH:33][C:34](=[O:39])[CH2:35][C:36]([OH:38])=O.C(Cl)CCl.C[N:45](C=O)C>CCOC(C)=O>[CH3:20][N:19]([CH3:21])[NH:18][C:16]([C:14]1[S:15][C:8]2[C:9](=[N:10][CH:11]=[CH:12][C:7]=2[O:6][C:5]2[CH:22]=[CH:23][C:2]([N:33]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[O:26][CH3:25])[C:34](=[O:39])[CH2:35][C:36]([NH2:45])=[O:38])=[CH:3][C:4]=2[F:24])[CH:13]=1)=[O:17]
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참가 물질

6

반응물 4

HCID 111,2-Dichloroethane2회HCID 6228DimethylformamideHCID 12664594N-(2-Methoxy-phenyl)-malonamic acid2회HCID 587902227-(4-amino-2-fluorophenoxy)-N',N'-dimethylthieno[3,2-b]pyridine-2-carbohydrazide

생성물 1

HCID 66649285N'-(4-(2-(2,2-Dimethylhydrazinecarbonyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N3-(2-methoxyphenyl)malonamide
수율 67%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

A solution of 7-(4-amino-2-fluorophenoxy)-N′,N′-dimethylthieno[3,2-b]pyridine-2-carbohydrazide 239 (200 mg, 0.578 mmol), 3-(2-methoxyphenylamino)-3-oxopropanoic acid 27 (195 mg, 0.693 mmol), and EDC (230 mg, 0.693 mmol) in DMF (8.3 mL) was stirred overnight at room temperature. More 27 (195 mg, 0.693 mmol) and EDC (230 mg, 0.693 mmol) were added and the mixture stirred 6 h more. The crude was diluted with EtOAc, extracted with water, over with anhydrous Na2SO4, and concentrated under reduced pressure. The residue was re dissolved in MeOH and purified twice by flash chromatography (DCM/MeOH 9:1) affording 236 (207 mg, 0.385 mmol, 67% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.60 (s, 1H), 9.94 (s, 0.5H), 9.63 (s, 1H), 9.49 (s, 0.5H), 8.57 (dd, J=5.5 Hz, J=7.2 Hz, 1H), 8.26 (m, 1H), 8.07 (d, J=7.4 Hz, 1H), 7.88 (d, J=12.9 Hz, 1H), 7.54-7.43 (m, 2H), 7.07 (m, 2H), 6.91 (m, 1H), 6.73 (m, 1H), 3.86 (s, 3H), 3.65 (s, 2H), 2.63 (s, 3H), 2.61 (s, 3H). MS (m/z): (M+1) 538.0 (100%).

후처리

  1. extractionextracted with water, over with anhydrous Na2SO4
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was re dissolved in MeOH
  4. custompurified twice by flash chromatography (DCM/MeOH 9:1)

출처 및 근거

ORD 기록
ord-71b0c3bcae564d468196cbbd766c5524
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08093264B2

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