1-Hydroxybenzotriazole → HCID 178461667、化合物

HRID 561965ノート

反応式

HRID 561965 の反応式
[Cl:1][C:2]1[N:3]=[C:4]([C@@H:15]([NH2:24])[C@H:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH3:17])[NH:5][C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([I:13])=[CH:9][C:8]=1[F:14].[C:25]([O:29][C:30]([NH:32][C@H:33]([C:37]1[CH:42]=[CH:41][C:40]([O:43][CH2:44][CH2:45][O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[CH:39][CH:38]=1)[C:34](O)=[O:35])=[O:31])([CH3:28])([CH3:27])[CH3:26].C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1>CN(C)C=O.O>[C:25]([O:29][C:30](=[O:31])[NH:32][C@H:33]([C:37]1[CH:38]=[CH:39][C:40]([O:43][CH2:44][CH2:45][O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[CH:41][CH:42]=1)[C:34](=[O:35])[NH:24][C@H:15]([C:4]1[NH:5][C:6]([C:7]2[CH:12]=[CH:11][C:10]([I:13])=[CH:9][C:8]=2[F:14])=[C:2]([Cl:1])[N:3]=1)[C@H:16]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[CH3:17])([CH3:27])([CH3:28])[CH3:26]

参加物

7

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66815165(R)-tert-butoxycarbonylamino-[4-(2-tert-butoxy-ethoxy)-phenyl]-acetic acidHCID 178461664(1S,2S)-1-[4-chloro-5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propylamine

生成物 1

HCID 178461667HCID 178461667、化合物収率 45.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (1S,2S)-1-[4-chloro-5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propylamine (550 mg, 1.21 mmol) in N,N-dimethylformamide (12 mL) was added (R)-tert-butoxycarbonylamino-[4-(2-tert-butoxy-ethoxy)-phenyl]-acetic acid (532 mg, 1.45 mmol) (prepared as described below), N,N-diisopropylethylamine (841 μL, 4.83 mmol), N-hydroxybenzotriazole (212 mg, 1.57 mmol) and O-benzotriazol-1-yl-N,N,N′N′-tetramethyluronium hexafluorophosphate (595 mg, 1.57 mmol). The mixture was stirred under an atmosphere of nitrogen at room temperature for 3 hours. The reaction was poured into water (20 mL) and extracted with ethyl acetate (2×25 mL). The organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography over silica gel gradient eluted with 20 to 50% v/v ethyl acetate/hexanes to give ((R)-[4-(2-tert-butoxy-ethoxy)-phenyl]-{(1S,2S)-1-[4-chloro-5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propylcarbamoyl}-methyl)-carbamic acid tert-butyl ester (440 mg, 45%).

後処理

  1. extractionextracted with ethyl acetate (2×25 mL)
  2. washwashed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by chromatography over silica gel gradient
  7. washeluted with 20 to 50% v/v ethyl acetate/hexanes

出典と根拠

ORDレコード
ord-2318c9bde447480186dd252c1aca44f3
出典データセット
uspto-grants-2011_11
特許番号
US08063085B2

反応ノート

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