Dichloromethane → 5-Bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-6-fluoro-1H-indole-7-carboxamide

HRID 387309

Reaction equation

HRID 387309 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:12]([NH2:14])=[O:13])[C:10]=1[F:11])[NH:7][CH:6]=[C:5]2[CH:15]1[CH2:20][CH2:19]S[CH2:17][CH2:16]1.C([O-])(O)=O.[Na+].O[O:27][S:28]([O-:30])=O.[K+].C(Cl)Cl>COCCOC.O.C(N(CC([O-])=O)CC(O)=O)CN(CC([O-])=O)CC(O)=O.[Na+].[Na+]>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:12]([NH2:14])=[O:13])[C:10]=1[F:11])[NH:7][CH:6]=[C:5]2[CH:15]1[CH2:20][CH2:19][S:28](=[O:30])(=[O:27])[CH2:17][CH2:16]1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 23707502Potassium hydroxy sulfiteHCID 593326735-Bromo-6-fluoro-3-(tetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide2×

Product 1

HCID 593326785-Bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-6-fluoro-1H-indole-7-carboxamideYield 19%

Reagents, catalysts & solvents 3

HCID 8759EDTA disodium saltCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

An aqueous solution of 0.0004 M Na2EDTA (0.882 mL, 0.353 μmol) was added to a solution of 5-Bromo-6-fluoro-3-(tetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (45 mg, 0.126 mmol) in DME (3 mL). In a separate flask, NaHCO3 (106 mg, 1.260 mmol) was added to a solution of Oxone (232 mg, 0.378 mmol) in water (1 mL). This mixture was then added in 3 portions over 3 min to the DME solution of 5-Bromo-6-fluoro-3-(tetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide. The reaction was stirred at room temperature for 17 h. Water (2 mL) and DCM (3 mL) were added, the layers were separated, and the aqueous layer was extracted with DCM (3×2 mL). The combined organic layers were washed with saturated NaCl (1×2 mL), dried (Na2SO4), filtered, and concentrated under a stream of nitrogen at 50° C. The residue was dried under high vacuum, giving 9.2 mg (19%) of the title compound.

Workup

  1. customthe layers were separated
  2. extractionthe aqueous layer was extracted with DCM (3×2 mL)
  3. washThe combined organic layers were washed with saturated NaCl (1×2 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under a stream of nitrogen at 50° C
  7. customThe residue was dried under high vacuum

Sources & evidence

ORD record
ord-482cd57ac7d64438b20f58dc92f7c8c8
Source dataset
uspto-grants-2013_02
Patent number
US08372875B2

Linked notes

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