N-Methylisatoic anhydride → 10-methyl-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione

HRID 1287564Notes

Reaction equation

HRID 1287564 reaction equation
[CH3:1][N:2]1[C:8](=[O:9])[O:7][C:5](=O)[C:4]2=[CH:10][CH:11]=[CH:12][CH:13]=[C:3]12.[NH:14]1[CH2:21][CH2:20][CH2:19][C@H:15]1C(O)=O>C(O)C>[CH3:1][N:2]1[C:3]2[CH:13]=[CH:12][CH:11]=[CH:10][C:4]=2[C:5](=[O:7])[N:14]2[CH2:21][CH2:20][CH2:19][CH:15]2[C:8]1=[O:9]

Participants

4

Reactant 2

HCID 25160N-Methylisatoic anhydrideHCID 145742L-Proline

Product 1

HCID 985943610-methyl-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 17.7 g. of N-methyl isatoic anhydride, 11.5 g. of L-proline and 250 ml. of ethanol is heated on a steam bath for three hours and then concentrated to remove the ethanol. The residue is mixed with benzene and a small portion of water and the layers are separated. The benzene layer is washed twice with water and concentrated to remove the solvent. The residue is triturated with ether. The crystals which form are collected by filtration and recrystallized from ethyl acetate yielding the pure dextrorotatory isomer, melting point 120°-122° C., [α]D25 + 486° (1%, methanol).

Workup

  1. additionA mixture of 17.7 g
  2. concentrationconcentrated
  3. customto remove the ethanol
  4. additionThe residue is mixed with benzene
  5. customa small portion of water and the layers are separated
  6. washThe benzene layer is washed twice with water
  7. concentrationconcentrated
  8. customto remove the solvent
  9. customThe residue is triturated with ether
  10. filtrationThe crystals which form are collected by filtration
  11. customrecrystallized from ethyl acetate yielding the pure dextrorotatory isomer, melting point 120°-122° C., [α]D25 + 486° (1%, methanol)

Sources & evidence

ORD record
ord-4ccd852600fd4f8983ec8849832fa68c
Source dataset
uspto-grants-1976_10
Patent number
US03985732

Reaction notes

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