Toluene → 2-[2-[4-[Bis(4-fluorophenyl)methyl]-1-piperidinyl]ethyl]-3,4-dihydro-1,4-dimethyl-1H-[1,3,5]-triazepino[3,2-a]benzimidazol-5(2H)-one

HRID 1031182Notes

Reaction equation

HRID 1031182 reaction equation
C1(C)C=CC=CC=1.Cl[CH2:9][CH2:10][CH:11]1[N:24]([CH3:25])[C:16]2=[N:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:15]2[C:14](=[O:26])[N:13]([CH3:27])[CH2:12]1.[F:28][C:29]1[CH:34]=[CH:33][C:32]([CH:35]([C:42]2[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=2)[CH:36]2[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)=[CH:31][CH:30]=1>C(N(CC)CC)C>[F:48][C:45]1[CH:46]=[CH:47][C:42]([CH:35]([C:32]2[CH:31]=[CH:30][C:29]([F:28])=[CH:34][CH:33]=2)[CH:36]2[CH2:41][CH2:40][N:39]([CH2:9][CH2:10][CH:11]3[N:24]([CH3:25])[C:16]4=[N:17][C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=5[N:15]4[C:14](=[O:26])[N:13]([CH3:27])[CH2:12]3)[CH2:38][CH2:37]2)=[CH:43][CH:44]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 132505444-[Bis(4-fluorophenyl)methyl]piperidine2×HCID 198197592-(2-Chloroethyl)-3,4-dihydro-1,4-dimethyl-1H-[1,3,5]triazepino[3,2-a]benzimidazol-5(2H)-one

Product 1

HCID 198197782-[2-[4-[Bis(4-fluorophenyl)methyl]-1-piperidinyl]ethyl]-3,4-dihydro-1,4-dimethyl-1H-[1,3,5]-triazepino[3,2-a]benzimidazol-5(2H)-one

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent2×

Procedure

To a solution of 50 mL of toluene containing 4.0 g (0.04 mol) of triethylamine was added 3.0 g (0.01 mol) of 2-(2-chloroethyl)-3,4-dihydro-1,4-dimethyl-1H-[1,3,5]triazepino[3,2-a]benzimidazol-5(2H)-one and 4.0 g (0.014 mol) of 4-[bis(4-fluorophenyl)methyl]piperidine. The mixture was heated to reflux for 3 days after which time 1.0 g (0.003 mL) of 4-[bis(4-fluorophenyl)methyl]piperidine and 1.0 g (0.01 mol) of triethylamine was added. Heating under reflux was continued for 24 hr. The solvent was removed by rotary evaporation and the residue dissolved in 100 mL of CH2Cl2. The organic phase was washed with 2×100 mL of 1N NaOH, dried over Na2SO4, filtered, and concentrated by rotary evaporation. The residue was subjected to preparative HPLC using silica gel as the stationary phase and eluting with ethanol. Combination of like fractions afforded 3.1 g (57%) of analytically pure material as a glass.

Workup

  1. temperatureThe mixture was heated
  2. additionwas added
  3. temperatureHeating
  4. temperatureunder reflux
  5. customThe solvent was removed by rotary evaporation
  6. dissolutionthe residue dissolved in 100 mL of CH2Cl2
  7. washThe organic phase was washed with 2×100 mL of 1N NaOH
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated by rotary evaporation
  11. washeluting with ethanol
  12. customCombination of like fractions afforded 3.1 g (57%) of analytically pure material as a glass

Sources & evidence

ORD record
ord-0d6fba876235442b8f3d154f78a4b27c
Source dataset
uspto-grants-1992_04
Patent number
US05109013

Reaction notes

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