Piperazine → HCID 59594377, compound

HRID 885002Notes

Reaction equation

HRID 885002 reaction equation
[Cl:1][C:2]1[C:3]2[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:4]=2[N:5]([CH3:10])[C:6](=[O:9])[CH2:7][N:8]=1.CC(C)([O-])C.[K+].[Br:22][C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[CH2:25]Br.N1CCNCC1>O1CCCC1>[Br:22][C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[CH2:25][CH:7]1[C:6](=[O:9])[N:5]([CH3:10])[C:4]2[CH:11]=[CH:12][C:13]([Cl:15])=[CH:14][C:3]=2[C:2]([Cl:1])=[N:8]1

Participants

6

Reactant 4

HCID 4837PiperazineHCID 769652-Bromobenzyl bromideHCID 123385855,7-Dichloro-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 59594377HCID 59594377, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

(E)-5,7-Dichloro-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one (400 mg, 1.65 mmol) was dissolved in anhydrous tetrahydrofuran (5 mL) under a nitrogen atmosphere, cooled to −78° C., then a 1 M solution of potassium tert-butoxide in tetrahydrofuran (1.7 mL, 1.7 mmol) was added dropwise. The reaction mixture was stirred for 10 minutes before a solution of the 2-bromobenzyl bromide (411 mg, 1.65 mmol) in tetrahydrofuran (2 mL) was added dropwise. The mixture was stirred at −78° C. for 20 minutes then the cooling bath removed and the mixture was allowed to warm to ambient temperature and stirred at ambient temperature for 18 hours. Piperazine (283 mg, 3.29 mmol) was added to remove excess 2-bromobenzyl bromide and the mixture was stirred at ambient temperature for 30 minutes, diluted with ethyl acetate, and washed with cold 1 M aqueous hydrogen chloride (2×40 mL). The organic layers were dried with sodium sulfate, decanted and concentrated in vacuo to approximately 20 mL of a red liquid. The product was purified on a short pad of silica gel eluting with 100 mL of ethyl acetate:hexanes (1:2) to yield (E)-3-(2-bromobenzyl)-5,7-dichloro-1-methyl-1H-benzo[e][1,4]diazepin-2(3H)-one (0.44 g, 65%). 1H NMR (300 MHz, CDCl3) δ 3.40 (s, 3H) 3.75 (m, 2H), 4.15 (m, 1H), 7.05-7.55 (m, 7H).

Workup

  1. additionwas added dropwise
  2. customthe cooling bath removed
  3. temperatureto warm to ambient temperature
  4. stirringstirred at ambient temperature for 18 hours
  5. customto remove excess 2-bromobenzyl bromide
  6. stirringthe mixture was stirred at ambient temperature for 30 minutes
  7. additiondiluted with ethyl acetate
  8. washwashed with cold 1 M aqueous hydrogen chloride (2×40 mL)
  9. dry with materialThe organic layers were dried with sodium sulfate
  10. customdecanted
  11. concentrationconcentrated in vacuo to approximately 20 mL of a red liquid
  12. customThe product was purified on a short pad of silica gel eluting with 100 mL of ethyl acetate:hexanes (1:2)

Sources & evidence

ORD record
ord-fc91a2fbec03438e92eccf97c92c893f
Source dataset
uspto-grants-2012_08
Patent number
US08242109B2

Reaction notes

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