Triethylamine → 1-(Adamant-1-yl)-3-(3-[2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)urea

HRID 412344

反応式

HRID 412344 の反応式
Cl.Cl.[NH2:3][C:4]1[CH:5]=[C:6]([CH:34]=[CH:35][CH:36]=1)[O:7][C:8]1[CH:9]=[CH:10][C:11]2[N:15]=[C:14]([CH2:16][O:17][C:18]3[CH:31]=[CH:30][C:21]([CH2:22][CH:23]4[S:27][C:26](=[O:28])[NH:25][C:24]4=[O:29])=[CH:20][CH:19]=3)[N:13]([CH3:32])[C:12]=2[CH:33]=1.[C:37]12([N:47]=[C:48]=[O:49])[CH2:46][CH:41]3[CH2:42][CH:43]([CH2:45][CH:39]([CH2:40]3)[CH2:38]1)[CH2:44]2.C(N(CC)CC)C>CN(C)C=O>[C:37]12([NH:47][C:48]([NH:3][C:4]3[CH:36]=[CH:35][CH:34]=[C:6]([O:7][C:8]4[CH:9]=[CH:10][C:11]5[N:15]=[C:14]([CH2:16][O:17][C:18]6[CH:31]=[CH:30][C:21]([CH2:22][CH:23]7[S:27][C:26](=[O:28])[NH:25][C:24]7=[O:29])=[CH:20][CH:19]=6)[N:13]([CH3:32])[C:12]=5[CH:33]=4)[CH:5]=3)=[O:49])[CH2:46][CH:41]3[CH2:42][CH:43]([CH2:45][CH:39]([CH2:40]3)[CH2:38]1)[CH2:44]2

参加物

5

反応物 3

HCID 8471TriethylamineHCID 20599951-IsocyanatoadamantaneHCID 865877725-[4-[6-(3-aminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride

生成物 1

HCID 185376501-(Adamant-1-yl)-3-(3-[2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)urea収率 13.9%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 5-[4-[6-(3-aminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride (400 mg), 1-adamantyl isocyanate (142 mg), triethylamine (153 mg) and anhydrous N,N-dimethylformamide (4 ml) was stirred at room temperature for 3 hours. 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→4:1→ethyl acetate as the eluant. The product insoluble in methanol was isolated by filtration and further purified by preparative reverse phase high performance liquid chromatography using acetonitrile:water=50:50→60:40→65:35→70:30 as the eluant to afford the title compound (66 mg, mp 227.1-231.4° C.).

後処理

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between ethyl acetate and water
  3. washThe extract was washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a silica gel column
  7. customThe product insoluble in methanol was isolated by filtration
  8. customfurther purified by preparative reverse phase high performance liquid chromatography

出典と根拠

ORDレコード
ord-dcb08689d66241e6a7ac9dfcfe826b4d
出典データセット
uspto-grants-2003_05
特許番号
US06562849B1

関連ノート

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