Hydroxyamine hydrochloride → (2'R,4'S,4'aS)-9',10'-difluoro-8'-[(E)-N-hydroxy-C-methylcarbonimidoyl]-2',4'-dimethylspiro[1,3-diazinane-5,5'-2,4,4a,6-tetrahydro-1H-[1,4]oxazino[4,3-a]quinoline]-2,4,6-trione

HRID 577814Notes

Reaction equation

[C:1]([C:4]1[CH:5]=[C:6]2[C:19](=[C:20]([F:23])[C:21]=1[F:22])[N:18]1[CH2:24][C@@H:25]([CH3:29])[O:26][C@@H:27]([CH3:28])[C@@H:17]1[C:8]1([C:13](=[O:14])[NH:12][C:11](=[O:15])[NH:10][C:9]1=[O:16])[CH2:7]2)(=O)[CH3:2].Cl.[NH2:31][OH:32]>CO>[F:22][C:21]1[C:20]([F:23])=[C:19]2[C:6]([CH2:7][C:8]3([C@H:17]4[C@H:27]([CH3:28])[O:26][C@H:25]([CH3:29])[CH2:24][N:18]42)[C:9](=[O:16])[NH:10][C:11](=[O:15])[NH:12][C:13]3=[O:14])=[CH:5][C:4]=1/[C:1](=[N:31]/[OH:32])/[CH3:2]

Participants

Conditions

Temperature: 85 °C

Procedure

To a solution of (2R,4S,4aS)-rel-8-acetyl-9,10-difluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione (Intermediate 12, 250 mg, 0.63 mmol) in MeOH, was added hydroxylamine hydrochloride (88 mg, 1.3 mmol) and the mixture heated to 85° C. for 12 hours. After cooling to room temperature, solvent was removed, and the residue was purified via normal phase HPLC (95:5: Hexane:IPA) to give the title compound as a racemic mixture in the form of a pale yellow solid. Yield: 50 mg (20%).

Workup

temperatureAfter cooling to room temperature
customsolvent was removed
customthe residue was purified via normal phase HPLC (95:5: Hexane:IPA)

Sources & evidence

ORD record: ord-17776ba6a62b413590565322a4daafa9
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040528B2

Reaction notes

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