1-Hydroxybenzotriazole → HCID 178461667, 화합물

HRID 561965노트

반응식

HRID 561965 반응식
[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]

참가 물질

7

반응물 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

생성물 1

HCID 178461667HCID 178461667, 화합물수율 45.2%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-2318c9bde447480186dd252c1aca44f3
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08063085B2

반응 노트

불러오는 중…