Methanol → 3-[(5,5-Dioxido-3,4-dihydro-2H-1,5-benzoxathiepin-8-yl)oxy]-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide

HRID 548771Notes

Reaction equation

HRID 548771 reaction equation
I[Si](C)(C)C.[O:6]=[S:7]1(=[O:41])[C:13]2[CH:14]=[CH:15][C:16]([O:18][C:19]3[CH:20]=[C:21]([CH:32]=[C:33]([O:35][C@@H:36]([CH3:40])[CH2:37][O:38]C)[CH:34]=3)[C:22]([NH:24][C:25]3[CH:30]=[N:29][C:28]([CH3:31])=[CH:27][N:26]=3)=[O:23])=[CH:17][C:12]=2[O:11][CH2:10][CH2:9][CH2:8]1.CO.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(#N)C>[O:41]=[S:7]1(=[O:6])[C:13]2[CH:14]=[CH:15][C:16]([O:18][C:19]3[CH:20]=[C:21]([CH:32]=[C:33]([O:35][C@@H:36]([CH3:40])[CH2:37][OH:38])[CH:34]=3)[C:22]([NH:24][C:25]3[CH:30]=[N:29][C:28]([CH3:31])=[CH:27][N:26]=3)=[O:23])=[CH:17][C:12]=2[O:11][CH2:10][CH2:9][CH2:8]1

Participants

6

Reactant 4

HCID 887MethanolHCID 24477Sodium ThiosulfateHCID 85247Trimethylsilyl iodideHCID 159499513-[(5,5-Dioxido-3,4-dihydro-2H-1,5-benzoxathiepin-8-yl)oxy]-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide

Product 1

HCID 159501203-[(5,5-Dioxido-3,4-dihydro-2H-1,5-benzoxathiepin-8-yl)oxy]-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamideYield 54.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Iodotrimethylsilane (0.416 mL, 2.92 mmol) was added to a solution of 3-[(5,5-dioxido-3,4-dihydro-2H-1,5-benzoxathiepin-8-yl)oxy]-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazin-2-yl)benzamide (150 mg, 0.29 mmol) in acetonitrile (7 mL) and the reaction stirred at RT overnight. Methanol (35 mL) was added, the reaction stirred for 1 hour, then a saturated aqueous solution of sodium thiosulphate (30 mL) was added and the reaction stirred for a further 20 minutes. The mixture was evaporated in vacuo, and the product was extracted away from the inorganic residues by the addition of 20% methanol in DCM (40 mL) with stirring. The organics were reduced in vacuo to a volume of approximately 5 mL. The residue was chromatographed on silica, eluting with 0-20% methanol in DCM, to give the desired compound as a cream solid (79 mg).

Workup

  1. stirringthe reaction stirred for 1 hour
  2. stirringthe reaction stirred for a further 20 minutes
  3. customThe mixture was evaporated in vacuo
  4. extractionthe product was extracted away from the inorganic residues by the addition of 20% methanol in DCM (40 mL)
  5. stirringwith stirring
  6. customThe residue was chromatographed on silica
  7. washeluting with 0-20% methanol in DCM

Sources & evidence

ORD record
ord-e162228840fb4e03bf8f8e800583be50
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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