Acetic Acid → 7,8-dimethoxy-1-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

HRID 1297093Notes

Reaction equation

[CH3:1][O:2][C:3]1[C:4]([O:16][CH3:17])=[CH:5][C:6]2[N:11]([CH3:12])[C:10](=[O:13])[O:9][C:8](=O)[C:7]=2[CH:15]=1.Cl.[NH2:19][CH2:20]C(OC)=O.CC(O)=O>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[C:4]([O:16][CH3:17])=[CH:5][C:6]2[N:11]([CH3:12])[C:10](=[O:13])[CH2:20][NH:19][C:8](=[O:9])[C:7]=2[CH:15]=1

Participants

Conditions

Temperature: 130 °C

Procedure

Heat under reflux for 6 hours a mixture of 320 mg (1.35 mmol) of 6,7-dimethoxy-1-methyl-1,2-dihydro-4H-3,1-benzoxazine-2,4-dione (XVI), 452 mg (3.24 mmol) of methyl glycinate hydrochloride in 4 ml of pyridine. Add 3 ml of AcOH and heat at 130° C. for 12 hours. Evaporate to dryness. Add 10 ml of a water-ice mixture. Allow to crystallize at 0° C. for 30 minutes. Filter and wash twice with 2 ml of H2O, twice with 1 ml of EtOH and twice with 5 ml of Et2O. Recrystallize in EtOH. One obtains 240 mg of the abovenamed product in the form of colorless crystals. Yield: 71%. M: 260–263° C. 1H-NMR (CDCl3, 300 MHz): d 3.42 (s, 3H, NCH3), 3.75–3.92 (m, 2H, CH2), 3.98 (s, 6H, 2×OCH3), 6.39 (s, 1H exchangeable, NH), 6.69 (s, 1H Ar), 7.37 (s, 1H Ar).

Workup

temperatureHeat
temperatureunder reflux for 6 hours
customEvaporate to dryness
additionAdd 10 ml of a water-ice mixture
customAllow to crystallize at 0° C. for 30 minutes
filtrationFilter
washwash twice with 2 ml of H2O, twice with 1 ml of EtOH and twice with 5 ml of Et2O
customRecrystallize in EtOH

Sources & evidence

ORD record: ord-59985eba395a4b2699df3809919da06d
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07250410B2

Reaction notes

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