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

HRID 519236Notes

Reaction equation

HRID 519236 reaction equation
C([O:3][C:4](=O)[C@H:5]([N:7]1[C:12]2[CH:13]=[C:14]([Br:17])[CH:15]=[CH:16][C:11]=2[O:10][CH2:9][C:8]1=S)[CH3:6])C.O.[NH2:21][NH2:22]>CCO>[Br:17][C:14]1[CH:13]=[C:12]2[C:11](=[CH:16][CH:15]=1)[O:10][CH2:9][C:8]1[N:7]2[CH:5]([CH3:6])[C:4](=[O:3])[NH:21][N:22]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 86727636(R)-2-(6-bromo-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

Product 1

HCID 867273756-Bromo-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-oneYield 9.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a mixture of (R)-2-(6-bromo-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (75.2 g, 219 mmol) in EtOH (800 mL) was added hydrazine hydrate (98%, 21.9 g, 438 mmol) and the mixture was stirred at ambient temperature overnight. The precipitate was collected by filtration and washed with cold EtOH (3×80 mL) to give 6-bromo-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (6 g, 9%) as a yellow solid. The filtrate was concentrated to give 70 g of crude product, which was purified by chromatography on silica gel (eluting with 10-25% EtOAc in petroleum ether) to give a second batch of (R)-6-bromo-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (45.9 g, 71%) as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.53 (brs, 1H), 7.10 (d, J=8.4 Hz, 1H), 7.03 (s, 1H), 6.89 (d, J=8.4 Hz, 1H), 4.69-4.52 (m, 3H), 1.52 (d, J=6.8 Hz, 3H). SFC (Table 1, Method 32) Rt=6.075 min.; [α]D20=−314.92 (C=0.002 g/mL in methanol).

Workup

  1. filtrationThe precipitate was collected by filtration
  2. washwashed with cold EtOH (3×80 mL)

Sources & evidence

ORD record
ord-9afd8bb3e07f4e5c8861ba168d79862d
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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