Dimethylamine → 4-[10-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazol-1-yl]-N,N,3-trimethylaniline

HRID 1628639Notes

Reaction equation

HRID 1628639 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:14]3=[N:15][C:16]4[C:21]([Cl:22])=[CH:20][CH:19]=[C:18]([CH:23]([CH2:26][CH3:27])[CH2:24][CH3:25])[C:17]=4[N:13]3[CH2:12][CH2:11][CH2:10][CH2:9]2)=[C:4]([CH3:28])[CH:3]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[CH3:56][NH:57][CH3:58]>C1(C)C=CC=CC=1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:22][C:21]1[C:16]2[N:15]=[C:14]3[N:8]([C:5]4[CH:6]=[CH:7][C:2]([N:57]([CH3:58])[CH3:56])=[CH:3][C:4]=4[CH3:28])[CH2:9][CH2:10][CH2:11][CH2:12][N:13]3[C:17]=2[C:18]([CH:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[CH:19][CH:20]=1

Participants

8

Reactant 4

HCID 674DimethylamineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 577863541-(4-Bromo-2-methylphenyl)-10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole

Product 1

HCID 577862424-[10-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazol-1-yl]-N,N,3-trimethylanilineYield 49%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1-(4-bromo-2-methylphenyl)-10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole (700 mg, 1.65 mmol), sodium tert-butoxide (396 mg, 4.13 mmol), 2-(di-tert-butylphosphino)biphenyl (39.4 mg, 0.132 mmol), tris(dibenzylideneacetone)dipalladium (151 mg, 0.165 mmol), and dimethylamine (2.0 M solution of tetrahydrofuran, 2.5 mL, 5.0 mmol) in toluene (2.5 ml) was stirred at 70° C. under nitrogen for 3 hr. The mixture was diluted with water, and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 0-30% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the solid, which was recrystallized from ethyl acetate/n-hexane to give the title compound as a colorless crystal (341 mg, 0.802 mmol, 49%).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel eluting with a 0-30% ethyl acetate/n-hexane gradient mixture
  7. concentrationThe filtrate was concentrated in vacuo
  8. customto give the solid, which
  9. customwas recrystallized from ethyl acetate/n-hexane

Sources & evidence

ORD record
ord-33540bd88b7e4d48833e5b6a540f2d61
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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