Water → 3-[6-(5-Methoxy-2-phenylindol-1-ylmethyl)pyridin-2-yl]-4,5-dihydro-1,2,4-thiadiazol-5-one

HRID 2400300Notes

Reaction equation

HRID 2400300 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]1[N:18]=[C:17]([C:19](=[N:21]O)[NH2:20])[CH:16]=[CH:15][CH:14]=1)[C:7]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[CH:6]2.[C:29](N1C=CN=C1)(N1C=CN=C1)=[S:30].[OH2:41]>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]1[N:18]=[C:17]([C:19]3[NH:20][C:29](=[O:41])[S:30][N:21]=3)[CH:16]=[CH:15][CH:14]=1)[C:7]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[CH:6]2

Participants

5

Reactant 3

HCID 962WaterHCID 802641,1'-ThiocarbonyldiimidazoleHCID 1363380916-(5-Methoxy-2-phenylindol-1-ylmethyl)pyridine-2-carboxamidoxime

Product 1

HCID 1363380943-[6-(5-Methoxy-2-phenylindol-1-ylmethyl)pyridin-2-yl]-4,5-dihydro-1,2,4-thiadiazol-5-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-(5-methoxy-2-phenylindol-1-ylmethyl)pyridine-2-carboxamidoxime (123 mg) in tetrahydrofuran (2 mL) was added 1,1′-thiocarbonyldiimidazole (71 mg). This mixture was stirred at room temperature for 1 hour. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. To the residue was added tetrahydrofuran (2 mL), and subsequently boron trifluoride ethyl ether complex (0.21 mL) was added thereto under ice-cooling. The mixture was stirred at room temperature for 3 days. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with 1 mol/L hydrochloric acid and water successively, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: dichloromethane-methanol) to obtain the title compound (24 mg). 1H-NMR (DMSO-d6) δ ppm: 3.77 (3H, s), 5.55 (2H, s), 6.45-6.55 (1H, m), 6.60-6.70 (1H, m), 6.77 (1H, dd, J=2.5, 8.9 Hz), 7.14 (1H, d, J=2.5 Hz), 7.28 (1H, d, J=8.9 Hz), 7.35-7.60 (5H, m), 7.75-7.95 (2H, m), 13.35 (1H, br s). ESI-MS (m/z): 415 (M+H)+

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. additionTo the residue was added tetrahydrofuran (2 mL), and subsequently boron trifluoride ethyl ether complex (0.21 mL)
  6. additionwas added
  7. temperatureunder ice-cooling
  8. stirringThe mixture was stirred at room temperature for 3 days
  9. additionTo the reaction mixture was added water
  10. extractionfollowed by extraction with ethyl acetate
  11. washThe organic layer was washed with 1 mol/L hydrochloric acid and water successively
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (eluting solvent: dichloromethane-methanol)

Sources & evidence

ORD record
ord-2c4f2dfc0514463e88c4398ea56dd822
Source dataset
uspto-grants-2014_08
Patent number
US08796247B2

Reaction notes

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