Nitrogen → (S)-7'-azido-4'-fluoro-2'-methoxy-5,6-dihydrospiro[[1,3]thiazine-4,9'-xanthen]-2-amine

HRID 931630Notes

Reaction equation

Br[C:2]1[CH:15]=[C:14]2[C:5]([O:6][C:7]3[C:8]([F:24])=[CH:9][C:10]([O:22][CH3:23])=[CH:11][C:12]=3[C@@:13]32[CH2:20][CH2:19][S:18][C:17]([NH2:21])=[N:16]3)=[CH:4][CH:3]=1.[N-:25]=[N+:26]=[N-:27].[Na+].CN[C@@H]1CCCC[C@H]1NC.N#N>[Cu]I.O.CCO>[N:25]([C:2]1[CH:15]=[C:14]2[C:5]([O:6][C:7]3[C:8]([F:24])=[CH:9][C:10]([O:22][CH3:23])=[CH:11][C:12]=3[C@@:13]32[CH2:20][CH2:19][S:18][C:17]([NH2:21])=[N:16]3)=[CH:4][CH:3]=1)=[N+:26]=[N-:27]

Participants

Conditions

Temperature: 90 °C

Procedure

To a disposable vial was charged with (S)-7′-bromo-4′-fluoro-2′-methoxy-5,6-dihydrospiro[[1,3]thiazine-4,9′-xanthen]-2-amine (300 mg, 0.733 mmol), copper(I) iodide (27.9 mg, 0.147 mmol), sodium azide (143 mg, 2.199 mmol) and (+)-sodium 1-ascorbate (14.52 mg, 0.073 mmol). EtOH (1.2 mL) and water (0.5 mL) were added followed by addition of trans-N,N′-dimethyl-1,2-cyclohexanediamine (34.7 μl, 0.220 mmol). The vial was capped and subjected to three cycles of evacuation-backfilling with N2. Finally it was heated in oil bath at 90° C. for 3 hrs. The reaction mixture was allowed to cool to RT. Excess of water was added and a tan precipitate formed. It was collected through Buchner funnel to yield (S)-7′-azido-4′-fluoro-2′-methoxy-5,6-dihydrospiro[[1,3]thiazine-4,9′-xanthen]-2-amine (170 mg, 0.458 mmol, 62.4% yield) as tan solid.

Workup

customThe vial was capped
temperatureto cool to RT
customa tan precipitate formed
customIt was collected through Buchner funnel

Sources & evidence

ORD record: ord-10eaefd9fbf9493b8842d7236cd0413e
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296759B2

Reaction notes

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