1,3-Benzodioxole-5-carboxylic acid → 1-(Benzo[1,3]dioxol-5-yl)-3-(3-[2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)urea

HRID 412345

반응식

HRID 412345 반응식
C(O)(=O)[C:2]1[CH:10]=[CH:9][C:8]2[O:7][CH2:6][O:5][C:4]=2[CH:3]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:20])C=CC=CC=1.C([N:32]([CH2:35]C)CC)C.Cl.Cl.[NH2:39][C:40]1[CH:41]=[C:42]([CH:70]=[CH:71][CH:72]=1)[O:43][C:44]1[CH:45]=[CH:46][C:47]2[N:51]=[C:50]([CH2:52][O:53][C:54]3[CH:67]=[CH:66][C:57]([CH2:58][CH:59]4[S:63][C:62](=[O:64])[NH:61][C:60]4=[O:65])=[CH:56][CH:55]=3)[N:49]([CH3:68])[C:48]=2[CH:69]=1>CN(C)C=O.C1(C)C=CC=CC=1>[O:7]1[C:8]2[CH:9]=[CH:10][C:2]([NH:32][C:35]([NH:39][C:40]3[CH:72]=[CH:71][CH:70]=[C:42]([O:43][C:44]4[CH:45]=[CH:46][C:47]5[N:51]=[C:50]([CH2:52][O:53][C:54]6[CH:67]=[CH:66][C:57]([CH2:58][CH:59]7[S:63][C:62](=[O:64])[NH:61][C:60]7=[O:65])=[CH:56][CH:55]=6)[N:49]([CH3:68])[C:48]=5[CH:69]=4)[CH:41]=3)=[O:20])=[CH:3][C:4]=2[O:5][CH2:6]1

참가 물질

7

반응물 4

HCID 71961,3-Benzodioxole-5-carboxylic acidHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 865877725-[4-[6-(3-aminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride

생성물 1

HCID 185376241-(Benzo[1,3]dioxol-5-yl)-3-(3-[2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)urea수율 5.6%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

A mixture of piperonylic acid (133 mg), diphenylphosphoryl azide (217 mg), triethylamine (314 mg) and anhydrous toluene (8 ml) was stirred at 80° C. for 1 hour. To the reaction mixture was added 5-[4-[6-(3-aminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride (400 mg) and anhydrous N,N-dimethylformamide (4 ml) at room temperature and the mixture was stirred at the same temperature for 1 hour and then allowed to stand overnight. The reaction mixture was concentrated and partitioned between ethyl acetate and water. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then concentrated. The residue was chromatographed on a silica gel column using ethyl acetate:n-hexane=3:1→1:0 as the eluant. The product insoluble in a mixture of methanol and diisopropyl ether (5:1) was isolated by filtration and was further purified by preparative reverse phase high performance liquid chromatography using acetonitrile/water=50:50 as the eluant to afford the title compound (26 mg, mp 179.2-182.4° C.).

후처리

  1. stirringthe mixture was stirred at the same temperature for 1 hour
  2. waitto stand overnight
  3. concentrationThe reaction mixture was concentrated
  4. custompartitioned between ethyl acetate and water
  5. washThe extract was washed with saturated aqueous sodium chloride solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was chromatographed on a silica gel column
  9. additionThe product insoluble in a mixture of methanol
  10. customdiisopropyl ether (5:1) was isolated by filtration
  11. customwas further purified by preparative reverse phase high performance liquid chromatography

출처 및 근거

ORD 기록
ord-b0c11f8d08bc412984da50e755ff0134
출처 데이터셋
uspto-grants-2003_05
특허 번호
US06562849B1

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