1-Hydroxybenzotriazole → HCID 178461667, compound

HRID 561965Notes

Reaction equation

HRID 561965 reaction equation
[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]

Participants

7

Reactant 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

Product 1

HCID 178461667HCID 178461667, compoundYield 45.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-2318c9bde447480186dd252c1aca44f3
Source dataset
uspto-grants-2011_11
Patent number
US08063085B2

Reaction notes

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