(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 → (2R,4S,4aS)-rel-11-fluoro-2,4,8-trimethyl-1,2,4,4a-tetrahydro-2'H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(1'H,3'H)-trione

HRID 245547Notes

Reaction equation

F[C:2]1[C:19]([F:20])=[C:18]2[C:5]([CH2:6][C:7]3([C@H:16]4[C@H:24]([CH3:25])[O:23][C@H:22]([CH3:26])[CH2:21][N:17]42)[C:12](=[O:13])[NH:11][C:10](=[O:14])[NH:9][C:8]3=[O:15])=[CH:4][C:3]=1/[C:27](=[N:29]/[OH:30])/[CH3:28]>CS(C)=O>[F:20][C:19]1[C:2]2[O:30][N:29]=[C:27]([CH3:28])[C:3]=2[CH:4]=[C:5]2[C:18]=1[N:17]1[CH2:21][C@@H:22]([CH3:26])[O:23][C@@H:24]([CH3:25])[C@@H:16]1[C:7]1([C:8](=[O:15])[NH:9][C:10](=[O:14])[NH:11][C:12]1=[O:13])[CH2:6]2

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of (2R,4S,4aS)-rel-9,10-difluoro-8-[(1E)-N-hydroxyethanimidoyl]-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 16, 250 mg, 0.63 mmol) in DMSO, was added K—O-t-Bu (47 mg, 0.636 mmol) and the mixture was heated to 120° C. for 12 hours. After cooling to room temperature and removal of solvent, the residue was purified using 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
customremoval of solvent
customthe residue was purified

Sources & evidence

ORD record: ord-6e41a9da8fa0460686bad06b03cb97e4
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658641B2

Reaction notes

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