Hydrazine hydrate (1:1) → (R)-4-methyl-6-nitro-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

HRID 519131Notes

Reaction equation

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

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of (R)-2-(6-nitro-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (150.0 g, 483.0 mmol) in ethanol (1.5 L) was added hydrazine hydrate (98%, 48.4 g, 967.0 mmol) and the reaction mixture was stirred at 25° C. for 16 h. The reaction mixture was filtered and the filter cake was washed with EtOH (3×100 mL) to give (R)-1-methyl-9-nitro-3,5-dihydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-2(1H)-one (100.0 g, 79%). SFC (Table 2, Method 4) Rt=3.19 min. 1H NMR (DMSO-d6, 400 MHz): δ 10.92 (s, 1H), 7.98 (d, J=2.4 Hz, 1H), 7.87 (dd, J=2.4, 8.8 Hz, 1H), 7.22 (d, J=8.8 Hz, 1H), 4.98 (q, J=6.8 Hz, 1H), 4.83-4.74 (d, J=12.8 Hz, 2H), 1.36 (d, J=6.8 Hz, 3H). The crude (R)-1-methyl-9-nitro-3,5-dihydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-2(1H)-one (33 g, 142 mmol, e.e. =77%) was dissolved in refluxing MeOH (2.1 L) and then cooled slowly to ambient temperature. The crystals were removed by filtration and the filtrate was concentrated in vacuo to give (R)-4-methyl-6-nitro-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (26 g, 79%) as a yellow solid. SFC (Table 2, Method 4) Rt=3.06 min, e.e. =98%.

Workup

filtrationThe reaction mixture was filtered
washthe filter cake was washed with EtOH (3×100 mL)

Sources & evidence

ORD record: ord-7ffdc12ad82d4885bdc9cb65cb1a579f
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115151B2

Reaction notes

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