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

HRID 1628648Notes

Reaction equation

HRID 1628648 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[C:22]1[C:27]([Cl:28])=[CH:26][C:25]([Cl: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>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:22]4[C:27]([Cl:28])=[CH:26][C:25]([Cl:29])=[CH:24][N:23]=4)[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

Participants

8

Reactant 4

HCID 14742,2'-BipyridineHCID 10796Cesium carbonateHCID 8170902-Bromo-3,5-dichloropyridineHCID 13610182510-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole

Product 1

HCID 5778619510-Chloro-1-(3,5-dichloropyridin-2-yl)-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazoleYield 34%

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; 100 mg, 0.34 mmol), 2-bromo-3,5-dichloropyridine (239 mg, 1.03 mmol), copper(I) iodide (65 mg, 0.34 mmol), 2,2′-bipyridyl (106 mg, 0.68 mmol) and cesium carbonate (222 mg, 0.68 mmol) in 1-methyl-2-pyrrolidinone (1.5 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 a solid, which was recrystallized from n-hexane/ethyl acetate to give the title compound (50 mg, 0.114 mmol, 34%) 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
  7. customto give a solid, which
  8. customwas recrystallized from n-hexane/ethyl acetate

Sources & evidence

ORD record
ord-609bb98bc55a4d4c9374603ac55ecbf6
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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