HCID 10872275, compound → Talampanel

HRID 1595170Notes

Reaction equation

HRID 1595170 reaction equation
[C:1]([N:4]1[C@H:10]([CH3:11])[CH2:9][C:8]2[CH:12]=[C:13]3[O:18][CH2:17][O:16][C:14]3=[CH:15][C:7]=2[C:6]([C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=2)=[N:5]1)(=[O:3])[CH3:2].[H][H]>C(O)C.[Pd].O.C(O)C>[C:1]([N:4]1[C@H:10]([CH3:11])[CH2:9][C:8]2[CH:12]=[C:13]3[O:18][CH2:17][O:16][C:14]3=[CH:15][C:7]=2[C:6]([C:19]2[CH:20]=[CH:21][C:22]([NH2:25])=[CH:23][CH:24]=2)=[N:5]1)(=[O:3])[CH3:2]

Participants

6

Reactant 2

HCID 10872275HCID 10872275, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 164509TalampanelYield 88.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 19096565Water ethanolSolvent

Procedure

(R)-7-acetyl-8,9-dihydro-8-methyl-5-(4-nitrophenyl)-7H-1,3-dioxolo[4,5-h][2,3]benzodiazepine (38.93 g) was hydrogenated in 730 mL (19 volumes) of 2B-3 ethanol using 7.79 g of 10% palladium on carbon and 1 atmosphere of hydrogen. When HPLC analysis indicated that starting material had been consumed, the catalyst was removed by filtration and the filtrate was evaporated to afford 38.7 g of crude product. The crude product was dissolved in 220 ML (5.7 volumes) of 1:1 water/ethanol by heating to reflux. The mixture was allowed to cool and the product precipitated near room temperature. The resulting thick, poorly stirring, slurry was stirred at room temperature and then cooled in an ice/water bath. The solid was isolated by filtration and dried in a vacuum oven at 55° C. overnight to afford 31.6 g of purified product. A second recrystallization using the same conditions afforded 28.7 g (30%) of product after drying under vacuum for 3 days at 65° C. and 3 days at room temperature. The product dried very slowly and 1.6% ethanol was still on the sample at this point. Analysis by X-ray diffraction (XRD), solid state NMR (SSNMR) and differential scanning calorimetry (DSC) indicated that the Form I polymorph was formed.

Workup

  1. customhad been consumed
  2. customthe catalyst was removed by filtration
  3. customthe filtrate was evaporated
  4. customto afford 38.7 g of crude product
  5. temperatureby heating to reflux
  6. temperatureto cool
  7. customthe product precipitated near room temperature
  8. stirringslurry was stirred at room temperature
  9. temperaturecooled in an ice/water bath
  10. customThe solid was isolated by filtration
  11. customdried in a vacuum oven at 55° C. overnight

Sources & evidence

ORD record
ord-37a8228bfeb1448a8776eaec5a78153a
Source dataset
uspto-grants-2001_09
Patent number
US06288057B1

Reaction notes

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