Pyridine → N-[(2R,4S,4aS)-rel-11-fluoro-2,4-dimethyl-2',4',6'-trioxo-1,1',2,3',4,4',4a,6'-octahydro-2'H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidin]-8-yl]acetamide

HRID 578011Notes

Reaction equation

N1C=CC=CC=1.[C:7](OC(=O)C)(=[O:9])[CH3:8].[NH2:14][C:15]1[C:19]2[CH:20]=[C:21]3[C:34](=[C:35]([F:36])[C:18]=2[O:17][N:16]=1)[N:33]1[CH2:37][C@@H:38]([CH3:42])[O:39][C@@H:40]([CH3:41])[C@@H:32]1[C:23]1([C:28](=[O:29])[NH:27][C:26](=[O:30])[NH:25][C:24]1=[O:31])[CH2:22]3>C(Cl)CCl>[F:36][C:35]1[C:18]2[O:17][N:16]=[C:15]([NH:14][C:7](=[O:9])[CH3:8])[C:19]=2[CH:20]=[C:21]2[C:34]=1[N:33]1[CH2:37][C@@H:38]([CH3:42])[O:39][C@@H:40]([CH3:41])[C@@H:32]1[C:23]1([C:28](=[O:29])[NH:27][C:26](=[O:30])[NH:25][C:24]1=[O:31])[CH2:22]2

Participants

Conditions

Temperature: 130 °C

Procedure

Pyridine (0.01 mL, 0.2 mmol) and acetic anhydride (0.10 mL, 0.14 mmol) were added sequentially to a solution of (2R,4S,4aS)-rel-8-amino-11-fluoro-2,4-dimethyl-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 (Example 1, 54 mg, 0.13 mmol) in ethylene dichloride, and the mixture was stirred at 130° C. for 12 hours. After cooling to room temperature, solvent was removed, and the residue was purified over a silica gel flash column using a gradient of methanol in chloroform to give the title compound as a racemic mixture in the form of a yellow solid. Yield: 7.5 mg, (13%).

Workup

temperatureAfter cooling to room temperature
customsolvent was removed
customthe residue was purified over a silica gel flash column

Sources & evidence

ORD record: ord-19a9af91d8bd4b8cbcb26a0df2242064
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040528B2

Reaction notes

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