Triethylamine → 5-Fluoro-2-(4-fluorophenoxy)-N-[4-(2H-tetrazol-5-YL)benzyl]benzamide

HRID 1293229ノート

反応式

HRID 1293229 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[C:6]([CH:10]=1)[C:7]([OH:9])=O.Cl.[N:20]1[NH:21][N:22]=[N:23][C:24]=1[C:25]1[CH:30]=[CH:29][C:28]([CH2:31][NH2:32])=[CH:27][CH:26]=1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>ClCCl.CN(C)C=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[C:6]([CH:10]=1)[C:7]([NH:32][CH2:31][C:28]1[CH:27]=[CH:26][C:25]([C:24]2[N:20]=[N:21][NH:22][N:23]=2)=[CH:30][CH:29]=1)=[O:9]

参加物

8

反応物 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 23224690(4-(1H-1,2,3,4-tetrazol-5-yl)phenyl)methanamine hydrochlorideHCID 433133155-Fluoro-2-(4-fluorophenoxy)benzoic acid

生成物 1

HCID 589053655-Fluoro-2-(4-fluorophenoxy)-N-[4-(2H-tetrazol-5-YL)benzyl]benzamide収率 73.1%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

A mixture of 5-fluoro-2-(4-fluorophenoxy)benzoic acid (120 mg, 0.48 mmol), 1-[4-(2H-tetrazol-5-yl)phenyl]methanamine hydrochloride (122 mg, 0.58 mmol), 1-hydroxy-1H-benztriazole monohydrate (110 mg, 0.72 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (138 mg, 0.72 mmol), and triethylamine (0.27 mL, 1.92 mmol) in dichloromethane (8 mL) and N,N-dimethylforamide (2 mL) was stirred at room temperature for 16 h. The mixture was diluted with dichloromethane (50 mL) and washed with 5% aqueous sodium dihydrogenphosphate solution (30 mL). The organic fraction was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by flush column chromatography on silica gel eluting with hexane/ethyl acetate/acetic acid (30:60:1) to afford 143 mg (73%) of the title compounds as white solids: 1H-NMR (DMSO-d6) δ 8.99 (1H, t, J=5.9 Hz), 7.91 (2H, d, J=8.2 Hz), 7.53–6.99 (8H, m), 4.50 (2H, d, J=5.9 Hz); MS (ESI) m/z 408 (M+H)+, 406 (M−H)−.

後処理

  1. washwashed with 5% aqueous sodium dihydrogenphosphate solution (30 mL)
  2. dry with materialThe organic fraction was dried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified
  5. customby flush column chromatography on silica gel eluting with hexane/ethyl acetate/acetic acid (30:60:1)

出典と根拠

ORDレコード
ord-d58a8944d83f435aa4f6553dccd45b20
出典データセット
uspto-grants-2007_07
特許番号
US07238714B2

反応ノート

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