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

HRID 1910690Notes

Reaction equation

HRID 1910690 reaction equation
Cl.[NH2:2][CH:3]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[Cl:14])[C:4]([OH:6])=O.[CH2:15](N(CC)CC)[CH3:16].C1([C:25]23[CH:35]=[C:34]([Cl:36])[CH:33]=[CH:32][CH:31]2[NH:30][C:29](=O)[O:28][C:26]3=O)CC1>O.C(#N)C>[Cl:36][C:34]1[CH:33]=[CH:32][C:31]2[N:30]([CH:29]3[CH2:16][CH2:15]3)[C:4](=[O:6])[CH:3]([CH2:7][C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[Cl:14])[NH:2][C:26](=[O:28])[C:25]=2[CH:35]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 112877902-Chlorophenylalanine hydrochlorideHCID 866641541-Cyclopropyl-5-chloroisatoic anhydride

Product 1

HCID 672835497-Chloro-3-(2-chlorobenzyl)-1-cyclopropyl-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dioneYield 2%

Reagents, catalysts & solvents 1

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

Procedure

2-Amino-3-(2-chlorophenyl)propanoic acid hydrochloride (4.97 g, 1 eq) was dissolved in water/acetonitrile (84 mL/84 mL) and triethylamine (5.91 mL, 2 eq) was then added. 1-Cyclopropyl-5-chloroisatoic anhydride (5.00 g, 1 eq) was then 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 (210 mL) and heated to 130° C. for 6 h. The crude mixture was then concentrated, and the residue was washed with NaHCO3(aq), stirring the mixture for a while before collecting the solid by filtration. The crude product was chromatographed (gradient: 3:1 hex:EtOAc to EtOAc) delivering the product (126 mg, 2% yield).

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 (210 mL)
  9. temperatureheated to 130° C. for 6 h
  10. concentrationThe crude mixture was then concentrated
  11. washthe residue was washed with NaHCO3(aq)
  12. stirringstirring the mixture for a while
  13. custombefore collecting the solid
  14. filtrationby filtration
  15. customThe crude product was chromatographed (gradient: 3:1 hex:EtOAc to EtOAc)

Sources & evidence

ORD record
ord-ccee1dab70dc40b1a7cc6352578eb688
Source dataset
uspto-grants-2013_12
Patent number
US08604023B2

Reaction notes

Loading…