Glycine → 1-Methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

HRID 718111Notes

Reaction equation

[CH3:1][N:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[C:5](=[O:12])[O:4][C:3]1=O.[NH2:14][CH2:15]C(O)=O.O.C(N(CC)CC)C>COCCOC.C(O)(=O)C.CCOCC>[CH3:1][N:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[C:5](=[O:12])[NH:14][CH2:15][C:3]1=[O:4]

Participants

Conditions

Temperature: 60 °C

Procedure

1-Methyl-1H-benzo[d][1,3]oxazine-2,4-dione (11.0 g, 62.1 mmol) and 2-aminoacetic acid (5.13 g, 68.3 mmol) were dissolved in DME (60 mL) and water (20 mL) and triethylamine was added. The reaction mixture was stirred at 60° C. for 4 hours. The mixture was concentrated in vacuo to get a light tan heavy oily residue that was dissolved in acetic acid (75 mL). This mixture was refluxed 4 hours then cooled down to room temperature. The solvent was evaporated to get a tan heavy oil. The oil was allowed to stand at room temperature overnight in ether (50 mL). The beige crystalline solid was filtered and washed with ether. The solid was then triturated in ether to afford title compound 467 (7.95 g, 67%) as a beige crystalline solid. 1H NMR (DMSO-d6) δ (ppm): 8.70 (s, 1H), 7.70 (d, J=7.6 Hz, 1H), 7.60 (t, J=7.2 Hz, 1H), 7.42 (d, J=8.0 Hz, 1H), 7.32 (t, J=7.5 Hz, 1H), 3.75-3.72 (m, 1H), 3.51-3.46 (m, 1H), 3.28 (s, 3H). MS (ESI): 190.90 (MH)+

Workup

concentrationThe mixture was concentrated in vacuo
customto get a light tan heavy oily residue that
temperatureThis mixture was refluxed 4 hours
temperaturethen cooled down to room temperature
customThe solvent was evaporated
customto get a tan heavy oil
filtrationThe beige crystalline solid was filtered
washwashed with ether
customThe solid was then triturated in ether

Sources & evidence

ORD record: ord-aa5c6682a1d04c6e935117a06971d5b2
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09193749B2

Reaction notes

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