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

HRID 920236Notes

Reaction equation

HRID 920236 reaction equation
[F:1][C:2]1[C:3]([S:24]([NH:27][C:28]2[S:32][N:31]=[CH:30][N:29]=2)(=[O:26])=[O:25])=[CH:4][C:5]2[O:9][C:8](=[O:10])[N:7]([CH2:11][C:12]3[C:21]4[CH2:20][C:19](=[O:22])[CH2:18][CH2:17][C:16]=4[CH:15]=[CH:14][CH:13]=3)[C:6]=2[CH:23]=1.C1COCC1.[BH4-].[Na+]>CO.O.CS(C)=O.C(O)(C(F)(F)F)=O>[F:1][C:2]1[C:3]([S:24]([NH:27][C:28]2[S:32][N:31]=[CH:30][N:29]=2)(=[O:25])=[O:26])=[CH:4][C:5]2[O:9][C:8](=[O:10])[N:7]([CH2:11][C:12]3[C:21]4[CH2:20][CH:19]([OH:22])[CH2:18][CH2:17][C:16]=4[CH:15]=[CH:14][CH:13]=3)[C:6]=2[CH:23]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 4311764Sodium borohydrideHCID 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

Product 1

HCID 715564855-fluoro-3-((7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)methyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 131734887H2O Dmso tfaSolvent

Procedure

In a vial was added 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) (29 mg, 0.061 mmol), followed by anhydrous THF (1 mL), then NaBH4 (8 mg, 0.211 mmol). The reaction mixture was then capped (not under N2) & stirred at room temperature. Followed by LC/MS. The reaction mixture was diluted with MeOH/drops of H2O/DMSO/TFA (lot of bubbling), filtered (syringe filter), then purified (without workup) 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 5-fluoro-3-((7-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)methyl)-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (21-1). HRMS [M+H] calculated; 477.0697, observed; 477.0705. 1H NMR (499 MHz, DMSO): δ 8.49 (s, 1H); 7.79 (d, J=5.5 Hz, 1H); 7.29 (d, J=9.6 Hz, 1H); 7.05-7.02 (m, 2H); 6.87-6.83 (m, 1H); 5.75 (s, 2H); 5.01-4.95 (m, 1H); 4.02-3.92 (m, 1H); 2.99-2.92 (m, 1H); 2.91-2.83 (m, 1H); 2.77-2.68 (m, 1H); 1.91-1.84 (m, 2H); 1.66-1.57 (m, 1H).

Workup

  1. customThe reaction mixture was then capped (not under N2) &
  2. filtrationfiltered
  3. filtration(syringe filter)
  4. custompurified (without workup) 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)
  5. concentrationdesired fractions concentrated (GENEVAC)
  6. dissolutiondissolved in MeOH/DCM
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-8a8882f25cd14c7bb7954c9f4b4bdf6d
Source dataset
uspto-grants-2016_03
Patent number
US09273040B2

Reaction notes

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