2,2'-Bipyridine → 1-(5-bromo-3-methylpyridin-2-yl)-10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole

HRID 1399226ノート

反応式

HRID 1399226 の反応式
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[NH:11][CH2:12][CH2:13][CH2:14][CH2:15][N:7]3[C:6]=2[C:5]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[CH:4][CH:3]=1.[Br:21][C:22]1[C:27]([CH3:28])=[CH:26][C:25]([Br:29])=[CH:24][N:23]=1.N1C=CC=CC=1C1C=CC=CN=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O.C(OCC)(=O)C.[Cu]I>[Br:29][C:25]1[CH:26]=[C:27]([CH3:28])[C:22]([N:11]2[C:8]3=[N:9][C:10]4[C:2]([Cl:1])=[CH:3][CH:4]=[C:5]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[C:6]=4[N:7]3[CH2:15][CH2:14][CH2:13][CH2:12]2)=[N:23][CH:24]=1.[Br:21][C:22]1[N:23]=[CH:24][C:25]([N:11]2[C:8]3=[N:9][C:10]4[C:2]([Cl:1])=[CH:3][CH:4]=[C:5]([CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])[C:6]=4[N:7]3[CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:26][C:27]=1[CH3:28]

参加物

9

反応物 4

HCID 14742,2'-BipyridineHCID 10796Cesium carbonateHCID 8176802,5-Dibromo-3-methylpyridineHCID 13610182510-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole

生成物 2

HCID 577860371-(6-bromo-5-methylpyridin-3-yl)-10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole収率 8%HCID 577864001-(5-bromo-3-methylpyridin-2-yl)-10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole収率 55%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 8857Ethyl Acetate溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
150 °C

実験手順

A mixture of 10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole (Reference example 72, 1.0 g, 3.42 mmol), 2,5-dibromo-3-methylpyridine (1.72 g, 6.85 mmol), copper(I) iodide (650 mg, 3.42 mmol), 2,2′-bipyridyl (1.07 g, 6.85 mmol) and cesium carbonate (2.23 g, 6.85 mmol) in 1-methyl-2-pyrrolidinone (10 mL) was stirred at 150° C. for 12 hr. The mixture was diluted with ethyl acetate, filtered through a pad of celite, washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 5-30% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give 1-(5-bromo-3-methylpyridin-2-yl)-10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole (870 mg, 55%) as a colorless solid and 1-(6-bromo-5-methylpyridin-3-yl)-10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole (130 mg, 8%) as a colorless solid.

後処理

  1. filtrationfiltered through a pad of celite
  2. washwashed with water and brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel eluting with a 5-30% ethyl acetate/n-hexane gradient mixture
  6. concentrationThe filtrate was concentrated in vacuo

出典と根拠

ORDレコード
ord-467e8c210a23405abfbd1a747be8ecfb
出典データセット
uspto-grants-2014_12
特許番号
US08901141B2

反応ノート

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