Dimethylamine → HCID 57786320, compound

HRID 1398997Notes

Reaction equation

HRID 1398997 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]([O:28][C:29]([F:32])([F:31])[F:30])[CH:3]=1.CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[CH3:60][NH:61][CH3:62]>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:61]([CH3:62])[CH3:60])=[CH:3][C:4]=4[O:28][C:29]([F:32])([F:30])[F:31])[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 57785936HCID 57785936, compound

Product 1

HCID 57786320HCID 57786320, compoundYield 47.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 1-[4-bromo-2-(trifluoromethoxy)phenyl]-10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazole (500 mg, 0.942 mmol), sodium tert-butoxide (226 mg, 2.35 mmol), 2-(di-tert-butylphosphino)biphenyl (22.4 mg, 0.0754 mmol), tris(dibenzylideneacetone)dipalladium (86.2 mg, 0.0942 mmol), and dimethylamine (2.0 M solution of tetrahydrofuran, 1.4 mL, 2.8 mmol) in toluene (1.4 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 0-20% 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 (221 mg, 0.446 mmol, 47%).

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 0-20% 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-14defbf9056f470db1167605313f69d3
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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