Tetrabutylammonium Fluoride → 3-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-[5-(3-hydroxy-3-methylbutyl)-2-thienyl]-1H-indole-7-carboxamide

HRID 656081Notes

Reaction equation

HRID 656081 reaction equation
[O:1]=[S:2]1(=[O:38])[CH2:7][CH2:6][CH:5]([C:8]2[C:16]3[C:11](=[C:12]([C:35]([NH2:37])=[O:36])[CH:13]=[C:14]([C:17]4[S:18][C:19]([CH2:22][CH2:23][C:24]([CH3:34])([O:26][Si](CC)(CC)CC)[CH3:25])=[CH:20][CH:21]=4)[CH:15]=3)[NH:10][CH:9]=2)[CH2:4][CH2:3]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[O:38]=[S:2]1(=[O:1])[CH2:3][CH2:4][CH:5]([C:8]2[C:16]3[C:11](=[C:12]([C:35]([NH2:37])=[O:36])[CH:13]=[C:14]([C:17]4[S:18][C:19]([CH2:22][CH2:23][C:24]([OH:26])([CH3:34])[CH3:25])=[CH:20][CH:21]=4)[CH:15]=3)[NH:10][CH:9]=2)[CH2:6][CH2:7]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium Fluoride2×HCID 593327423-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-(5-{3-methyl-3-[(triethylsilyl)oxy]butyl}-2-thienyl)-1H-indole-7-carboxamide

Product 1

HCID 593326803-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-[5-(3-hydroxy-3-methylbutyl)-2-thienyl]-1H-indole-7-carboxamideYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-(5-{3-methyl-3-[(triethylsilyl)oxy]butyl}-2-thienyl)-1H-indole-7-carboxamide (55 mg, 0.1 mmol) was dissolved in tetrahydrofuran (3 mL). Tetrabutylammonium fluoride (1 M in THF, 0.3 mL, 0.3 mmol) was added and the mixture was stirred at rt for 2 h. Additional TBAF (1 M in THF, 0.7 mL, 0.7 mmol) was added, and the mixture was stirred at 45° C. overnight. The reaction mixture was concentrated, re-diluted in dichloromethane (20 mL), and washed with water (20 mL). The organic layer was dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography, eluting with 0-15% methanol in dichloromethane. The residue was then repurified by Gilson HPLC (NH4OH buffer). The product fractions were combined and concentrated in an EZ2 Genevac evaporator, giving 17 mg (40%) of the title compound.

Workup

  1. stirringthe mixture was stirred at 45° C. overnight
  2. concentrationThe reaction mixture was concentrated
  3. additionre-diluted in dichloromethane (20 mL)
  4. washwashed with water (20 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography
  8. washeluting with 0-15% methanol in dichloromethane
  9. customThe residue was then repurified by Gilson HPLC (NH4OH buffer)
  10. concentrationconcentrated in an EZ2 Genevac evaporator

Sources & evidence

ORD record
ord-b5ab1df35c15449fa65d6112e489841f
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

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