Triethylamine → 3H-1,5-Benzodiazepine, 2,4-bis(4-methyl-1-piperazinyl)-3-propylidene-

HRID 1782399Notes

Reaction equation

HRID 1782399 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]([CH:26](O)[CH2:27][CH3:28])[C:10]([N:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)=[N:11][C:12]3[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=3[N:14]=2)[CH2:4][CH2:3]1.C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O.[OH-].[Na+]>ClCCl.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CO>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([C:8]2[C:9](=[CH:26][CH2:27][CH3:28])[C:10]([N:19]3[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]3)=[N:11][C:12]3[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=3[N:14]=2)[CH2:6][CH2:7]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 14798Sodium HydroxideHCID 100238171-[2,4-bis (4-methyl-1-piperazinyl)-3H-[1,5]benzodiazepin-3-yl]-1-propanol

Product 1

HCID 102492283H-1,5-Benzodiazepine, 2,4-bis(4-methyl-1-piperazinyl)-3-propylidene-Yield 76%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of 1-[2,4-bis(4-methyl-1-piperazinyl)-3H-[1,5]benzodiazepin-3-yl]-1-propanol (19.93 g, 50 mmol) and triethylamine (45 ml, 325 mmol) in dichloromethane (100 ml) under constant flow of argon, at 0° C., a solution of trifluoroacetic anhydride (21 ml, 150 mmol) in dichloromethane (50 ml) was added dropwise. The reaction mixture was stirred for another hour at 0° C. The solution was allowed to warm to room temperature. Methanol (66 ml) and tetrabutylammonium bromide (1.61 g, 5 mmol) were added successively. While strongly agitated NaOH (1 M, 660 ml) was added dropwise. Two phase system was agitated for two hours. The phases were separated and the water phase was extracted with dichloromethane (2×100 ml). The organic phase was dried over anhydrous Na2SO4 and the solvent was evaporated at reduced pressure. The crude product was suspended in isopropyl ether (150 ml) and filtered off the filtrate was evaporated at reduced pressure to give 14.44 g (76%) of the title compound as a brown resin.

Workup

  1. temperatureto warm to room temperature
  2. stirringTwo phase system was agitated for two hours
  3. customThe phases were separated
  4. extractionthe water phase was extracted with dichloromethane (2×100 ml)
  5. dry with materialThe organic phase was dried over anhydrous Na2SO4
  6. customthe solvent was evaporated at reduced pressure
  7. filtrationfiltered off the filtrate
  8. customwas evaporated at reduced pressure

Sources & evidence

ORD record
ord-1e0c4f3c945e4e7e8a516efbac4e0901
Source dataset
uspto-grants-2009_03
Patent number
US07498433B2

Reaction notes

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