Hydrochloric Acid → N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine

HRID 1619634Notes

Reaction equation

HRID 1619634 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[CH:4][N:3]=1.[CH3:7][O:8][C:9]1[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][C:10]=1[CH:11]=O.[BH4-].[Na+].Cl.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH3:7][O:8][C:9]1[CH:16]=[C:15]([O:17][CH3:18])[CH:14]=[CH:13][C:10]=1[CH2:11][NH:1][C:2]1[S:6][N:5]=[CH:4][N:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 691752,4-DimethoxybenzaldehydeHCID 2902745-Amino-1,2,4-thiadiazoleHCID 4311764Sodium borohydride

Product 1

HCID 57732216N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amineYield 49.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 5-amino-1,2,4-thiadiazole (1 g, 9.89 mmol) and 2,4-dimethoxybenzaldehyde (1.81 g, 10.9 mmol) in toluene (30 mL) was refluxed under Dean-Stark conditions for 2 hours. The reaction mixture was evaporated and the residue taken up in methanol (25 mL), sodium borohydride (600 mg, 15.9 mmol) was added carefully in small portions (vigorous effervescence after each addition), and the reaction was left to stir for 18 hours at ambient temperature. A 2M aqueous solution of hydrogen chloride (1 mL) was added followed by a 2M aqueous solution of sodium hydroxide (10 mL). The bulk of the methanol was evaporated, water (20 mL) was added and the mixture extracted with ethyl acetate (2×30 mL). The combined organic phase was washed with brine (20 mL), dried, and concentrated in vacuo. The residue was purified by silica gel column chromatography (ISCO™ column 120 g; 25-60% ethyl acetate in heptane gradient elution) to furnish a semi-solid residue that was re-evaporated from heptane. tert-Butylmethyl ether (2-3 mL) was added, followed by heptane (2-3 mL). The resulting solid was collected by filtration, washed with heptane and dried to afford the title compound (1.22 g).

Workup

  1. temperaturewas refluxed under Dean-Stark conditions for 2 hours
  2. customThe reaction mixture was evaporated
  3. additionafter each addition), and the reaction
  4. waitwas left
  5. customThe bulk of the methanol was evaporated
  6. additionwater (20 mL) was added
  7. extractionthe mixture extracted with ethyl acetate (2×30 mL)
  8. washThe combined organic phase was washed with brine (20 mL)
  9. customdried
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by silica gel column chromatography (ISCO™ column 120 g; 25-60% ethyl acetate in heptane gradient elution)
  12. customto furnish a semi-solid residue that
  13. customwas re-evaporated from heptane
  14. additiontert-Butylmethyl ether (2-3 mL) was added
  15. filtrationThe resulting solid was collected by filtration
  16. washwashed with heptane
  17. customdried

Sources & evidence

ORD record
ord-67a8d4e48a9b4113a27d6b161785b718
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

Loading…