Trifluoroacetic acid → 5-Fluoro-2-oxo-3-((7-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)methyl)-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

HRID 920233Notes

Reaction equation

HRID 920233 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[CH2:11][N:12]2[C:16]3[CH:17]=[C:18]([F:41])[C:19]([S:21]([N:24](CC4C=CC(OC)=CC=4OC)[C:25]4[S:29][N:28]=[CH:27][N:26]=4)(=[O:23])=[O:22])=[CH:20][C:15]=3[O:14][C:13]2=[O:42])[CH2:4][CH2:3][C:2]21OCC[O:43]2.C(O)(C(F)(F)F)=O>C(Cl)Cl.CS(C)=O.CO>[F:41][C:18]1[C:19]([S:21]([NH:24][C:25]2[S:29][N:28]=[CH:27][N:26]=2)(=[O:22])=[O:23])=[CH:20][C:15]2[O:14][C:13](=[O:42])[N:12]([CH2:11][C:9]3[C:10]4[CH2:1][C:2](=[O:43])[CH2:3][CH2:4][C:5]=4[CH:6]=[CH:7][CH:8]=3)[C:16]=2[CH:17]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 895263363-((3',4'-Dihydro-1'H-spiro[[1,3]dioxolane-2,2'-naphthalen]-8'-yl)methyl)-N-(2,4-dimethoxybenzyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Product 1

HCID 895260585-Fluoro-2-oxo-3-((7-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)methyl)-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22036561Dimethyl sulfoxide methanolSolvent

Procedure

To a flask containing 3-((3′,4′-dihydro-1′H-spiro[[1,3]dioxolane-2,2′-naphthalen]-8′-yl)methyl)-N-(2,4-dimethoxybenzyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (19-4) (1.65 g, 2.467 mmol) in DCM (10 ml) was added TFA (8 ml, 104 mmol). The reaction mixture (clear pink/purple with R2 addition) was then capped (not under N2) & stirred at room temperature. Followed by LC/MS . . . added 3 additional portions of TFA then after several hours at room temperature the reaction mixture was diluted with DMSO/MeOH, then concentrated (to remove DCM), then filtered to yield a portion of 5-fluoro-2-oxo-3-((7-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)methyl)-N-(1,2,4-thiadiazazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (19-5). The filtrate was then purified by reverse phase chromatography (5-75% MeCN/H2O; 0.1% TFA in AQ; 20 min gradient; Waters 30×150 mm Sunfire 5 micron C18 column); desired fractions concentrated (GENEVAC), then dissolved in MeOH/DCM & concentrated to yield another portion of 5-fluoro-2-oxo-3-((7-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)methyl)-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (19-5). HRMS [M+H] calculated; 475.0541, observed; 475.0528.

Workup

  1. additionThe reaction mixture (clear pink/purple with R2 addition)
  2. customwas then capped (not under N2) &
  3. concentrationconcentrated
  4. custom(to remove DCM)
  5. filtrationfiltered

Sources & evidence

ORD record
ord-ce1f26752c554100b309018ce40954c7
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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