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

HRID 1399006Notes

Reaction equation

HRID 1399006 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]([CH3:28])=[CH:26][C:25]([N+:29]([O-:31])=[O:30])=[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]([CH3:28])=[CH:26][C:25]([N+:29]([O-:31])=[O:30])=[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 52004662-Bromo-3-methyl-5-nitropyridineHCID 13610182510-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole

Product 1

HCID 5778632310-Chloro-7-(1-ethylpropyl)-1-(3-methyl-5-nitropyridin-2-yl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazoleYield 40%

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; 292 mg, 1.00 mmol), 2-bromo-3-methyl-5-nitropyridine (651 mg, 3.00 mmol), copper(I) iodide (190 mg, 1.00 mmol), 2,2′-bipyridyl (312 mg, 2.00 mmol) and cesium carbonate (652 mg, 2.00 mmol) in 1-methyl-2-pyrrolidinone (3.0 mL) was stirred at 150° C. for 16 hr. The mixture was diluted with ethyl acetate, filtered through a pad of celite, washed with 1N hydrochloric acid 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 (170 mg, 0.397 mmol, 40%) as a yellow solid.

Workup

  1. filtrationfiltered through a pad of celite
  2. washwashed with 1N hydrochloric acid 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-c22642af0a7a4e0ba74d2ae4a995fba4
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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