Hydrochloric Acid → 1-{6-[10-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazol-1-yl]-5-methylpyridin-3-yl}ethanone

HRID 1399230Notes

Reaction equation

HRID 1399230 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:16]4[N:21]=[CH:20][C:19](C#N)=[CH:18][C:17]=4[CH3:24])[CH2:12][CH2:13][CH2:14][CH2:15][N:7]3[C:6]=2[C:5]([CH:25]([CH2:28][CH3:29])[CH2:26][CH3:27])=[CH:4][CH:3]=1.[CH3:30][Li].Cl.[C:33](=[O:36])(O)[O-].[Na+]>O1CCCC1>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:16]4[N:21]=[CH:20][C:19]([C:33](=[O:36])[CH3:30])=[CH:18][C:17]=4[CH3:24])[CH2:12][CH2:13][CH2:14][CH2:15][N:7]3[C:6]=2[C:5]([CH:25]([CH2:26][CH3:27])[CH2:28][CH3:29])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 577859886-[10-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazol-1-yl]-5-methylpyridine-3-carbonitrileHCID 178418348HCID 178418348, compound

Product 1

HCID 577858891-{6-[10-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazol-1-yl]-5-methylpyridin-3-yl}ethanoneYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A mixture of 6-[10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazol-1-yl]-5-methylpyridine-3-carbonitrile (90 mg, 0.22 mmol) in tetrahydrofuran (2 mL) was added methyllithium (1.8 M solution in ether, 0.61 mL, 1.10 mmol) at −78° C. After stirring for 1 hr at −78° C., 1 N hydrochloric acid was added and the mixture was warmed to room temperature during 15 min. Aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. Organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 20-50% ethyl acetate/n-hexane gradient mixture followed by recrystallization from ethyl acetate/n-hexane to afford the title compound (70 mg, 67%) as a colorless solid.

Workup

  1. temperaturethe mixture was warmed to room temperature during 15 min
  2. extractionthe mixture was extracted with ethyl acetate
  3. washOrganic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel eluting with a 20-50% ethyl acetate/n-hexane gradient mixture
  7. customfollowed by recrystallization from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-c80bf03d2087461482ec04c8b32f6085
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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