Triethylamine → 7-Chloro-3-(2-chlorophenethyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

HRID 1910681Notes

Reaction equation

HRID 1910681 reaction equation
Cl.[NH2:2][CH:3]([CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[Cl:15])[C:4]([OH:6])=O.C(N(CC)CC)C.[Cl:23][C:24]1[CH:35]=[C:28]2[C:29](OC(=O)[NH:33][C:27]2=[CH:26][CH:25]=1)=[O:30]>O.C(#N)C>[Cl:23][C:24]1[CH:25]=[CH:26][C:27]2[NH:33][C:4](=[O:6])[CH:3]([CH2:7][CH2:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[Cl:15])[NH:2][C:29](=[O:30])[C:28]=2[CH:35]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 784805-Chloroisatoic anhydrideHCID 672826112-Amino-4-(2-chlorophenyl)butanoic acid hydrochloride

Product 1

HCID 672831157-Chloro-3-(2-chlorophenethyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

2-Amino-4-(2-chlorophenyl)butanoic acid hydrochloride (1.49 g, 1 eq) was dissolved in water/acetonitrile 1:1 (24 mL:24 mL), and triethylamine (1.67 mL, 2 eq) was then added. 5-Chloroisatoic anhydride (1.18 g, 1 eq) was added in about 10 portions giving time between each addition for the previous portion to dissolve. After all of the anhydride was added the reaction was stirred at room temperature overnight. Any solids present after reaction were filtered off. The filtrate was concentrated in vacuo, azeotroped with acetonitrile, re-dissolved in AcOH (60 mL) and heated to 130° C. for 6 h. The crude mixture was then concentrated, and the residue was rinsed with NaHCO3(aq), stirring the slurry for 30 minutes before collecting the solid by filtration. The crude solid was washed with acetonitrile. 1H-NMR (300 MHz, DMSO-d6) δ 10.50 (s, 1H), 8.74 (d, 1H), 7.68 (s, 1H), 7.59 (d, 1H), 7.40-7.03 (m, 5H), 3.66 (q, 1H), 2.75 (m, 2H), 2.03 (m, 1H), 1.83 (m, 1H). MS (ES+) m/z 371.0 (M+Na).

Workup

  1. customgiving time
  2. additionbetween each addition for the previous portion
  3. dissolutionto dissolve
  4. customafter reaction
  5. filtrationwere filtered off
  6. concentrationThe filtrate was concentrated in vacuo
  7. customazeotroped with acetonitrile
  8. dissolutionre-dissolved in AcOH (60 mL)
  9. temperatureheated to 130° C. for 6 h
  10. concentrationThe crude mixture was then concentrated
  11. washthe residue was rinsed with NaHCO3(aq)
  12. stirringstirring the slurry for 30 minutes
  13. custombefore collecting the solid
  14. filtrationby filtration
  15. washThe crude solid was washed with acetonitrile

Sources & evidence

ORD record
ord-8f03681721014ee09bd6b87a26e30307
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

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