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 1628872Notes

Reaction equation

HRID 1628872 reaction equation
[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]

Participants

9

Reactant 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

Product 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]benzimidazoleYield 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]benzimidazoleYield 55%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-52afec2fc58246edb0f2ecfc2523ec3a
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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