Acetic Acid → 3-amino-1H-1,5-benzodiazepine-2,4(3H,5H)-dione

HRID 131365Notes

Reaction equation

HRID 131365 reaction equation
C(O)(=O)C.CO[N:7]=[C:8]1[C:14](=[O:15])[NH:13][C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[NH:10][C:9]1=[O:20]>[Pd].C(OCC)(=O)C>[NH2:7][CH:8]1[C:14](=[O:15])[NH:13][C:12]2[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=2[NH:10][C:9]1=[O:20]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 190708143-Methoxyimino-1H-1,5-benzodiazepine-2,4(3H,5H)-dione

Product 1

HCID 219558063-amino-1H-1,5-benzodiazepine-2,4(3H,5H)-dioneYield 84%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Wet 10% Pd/C (37.5 g) with glacial acetic acid (HOAc, 3.75 L). Add 1,5-dihydro-benzo[b][1,4]diazepine-2,3,4-trione 3-(O-methyl-oxime) (150 g, 0.684 mol), and subject the resulting mixture to catalytic hydrogenation under 50 psi H2 at ambient temperature for ˜18 hours until complete by HPLC. Remove the catalyst by filtration over glass fiber paper/Hyflo and rinse with HOAc (2 L). Concentrate the filtrate in vacuo to obtain the crude product as an amber waxy solid. Treat the solid with ethyl acetate (EtOAc, 3 L) and heat to 70° C. with stirring for 1 hour. Allow the slurry to cool to ambient temperature, then force cool to 0° C. Isolate the product by filtration and dry to afford 109.9 g (84%) of the title compound: 1H NMR (300 MHz, DMSO-d6) δ 10.48 (bs, 2H), 7.18 (m, 4H), 3.75 (s, 1H), ˜3.5 (bs, 2H); 13C NMR (75 MHz, DMSO-d6) δ 167.9, 164.5, 129.2, 125.1, 122.2, 55.8, 55.7; IR (KBr) 3375, 3306, 3282, 3047, 2750, 1697, 1670, 1559, 1500, 1433, 1411, 1337, 1307, 1258, 1183 cm−1; V (EtOH) λmax 217 nm (ε 33772), 285 nm (ε 3210); HRMS (ES+) exact mass calc'd for C9H9N3O2 192.0773, Found 192.0768.

Workup

  1. customat ambient temperature
  2. customfor ˜18 hours
  3. customRemove the catalyst
  4. filtrationby filtration over glass fiber paper/Hyflo
  5. washrinse with HOAc (2 L)
  6. concentrationConcentrate the filtrate in vacuo
  7. customto obtain the crude product as an amber waxy solid
  8. temperatureto cool to ambient temperature
  9. temperatureforce cool to 0° C
  10. customIsolate the product
  11. filtrationby filtration
  12. customdry

Sources & evidence

ORD record
ord-ab744c8213f6411e8a3b4287f0297f31
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

Loading…