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

HRID 1782397Notes

Reaction equation

HRID 1782397 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH2:9][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.[CH:26]([N-]C(C)C)([CH3:28])[CH3:27].[Li+].C(=O)CC.C(N(CC)CC)C.N1C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.[OH-].[Na+]>O1CCCC1.CO>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([C:8]2[C:9](=[CH:27][CH2:26][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

10

Reactant 7

HCID 527PropanalHCID 1049PyridineHCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 14798Sodium HydroxideHCID 2724682Lithium diisopropylamideHCID 117248372,4-Bis(4-methyl-1-piperazinyl)-3H-1,5-benzodiazepine

Product 1

HCID 102492283H-1,5-Benzodiazepine, 2,4-bis(4-methyl-1-piperazinyl)-3-propylidene-Yield 36,843.398%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-30 °C

Procedure

A suspension of 2,4-bis(4-methyl-1-piperazinyl)-3H-[1,5]benzodiazepine (1.702 g, 5 mmol) in tetrahydrofuran (20 ml) under constant flow of argon was cooled to −30° C. A solution of lithium diisopropylamide (LDA) (2 M, 3.75 ml, 7.5 mmol) was added dropwise. Thus obtained dark brown suspension was allowed to warm to −5° C. until dissolved and then again cooled to −30° C. Propionaldehyd (0.54 ml, 7.5 mmol) was added during 5 min. The resulting clear yellow solution was allowed to warm to −5° C., triethylamine (5.55 ml, 40 mmol) and pyridine (0.040 ml, 0.5 mmol) were added. A solution of trifluoroacetic anhydride (4.2 ml, 30 mmol) in tetrahydrofuran (6 ml) was added dropwise maintaining the temperature at −5° C. The reaction mixture was stirred for another hour. Methanol (5 ml) and while strongly agitated NaOH (1 M, 35 ml) were added dropwise. The reaction mixture was stirred for four hours while slowly warming to room temperature. The solution was made acidic at ph of 1 and extracted with dichloromethane (3×25 ml). The water phase was made alkalic at a pH of 10 and extracted with diethyl ether (15×25 ml). After each extraction water phase was adjusted to pH of 10. The ether phase was dried over anhydrous Na2SO4 and ether was evaporated at reduced pressure to give 1, 701 g (89%) of the title compound as a yellow resin.

Workup

  1. temperatureto warm to −5° C.
  2. dissolutionuntil dissolved
  3. temperatureagain cooled to −30° C
  4. temperatureto warm to −5° C.
  5. temperaturemaintaining the temperature at −5° C
  6. stirringThe reaction mixture was stirred for four hours
  7. temperaturewhile slowly warming to room temperature
  8. extractionextracted with dichloromethane (3×25 ml)
  9. extractionextracted with diethyl ether (15×25 ml)
  10. extractionAfter each extraction water phase
  11. dry with materialThe ether phase was dried over anhydrous Na2SO4 and ether
  12. customwas evaporated at reduced pressure

Sources & evidence

ORD record
ord-b122cf529c28402ba6b23f656be4f042
Source dataset
uspto-grants-2009_03
Patent number
US07498433B2

Reaction notes

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