Hydrochloric Acid → (2,4-dimethoxy-benzyl)[1,2,4]thiadiazol-5-yl-amine N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine

HRID 509108Notes

Reaction equation

HRID 509108 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.[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 86643827(2,4-dimethoxy-benzyl)[1,2,4]thiadiazol-5-yl-amine N-(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), NaBH4 (600 mg, 15.9 mmol) was added carefully in small portions (vigorous effervescence after each addition), and the reaction was left stirring overnight at ambient temperature. Aqueous HCl (2M, 1 mL) was added followed by aqueous NaOH (2M, 10 mL). The bulk of the methanol was evaporated, water (20 mL) added and extracted with ethyl acetate (2×30 mL). The combined organic was washed brine (20 mL), dried, and evaporated. 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, 49%).

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) added
  7. extractionextracted with ethyl acetate (2×30 mL)
  8. washThe combined organic was washed brine (20 mL)
  9. customdried
  10. customevaporated
  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-33de0faf38804f05938033ad276f2844
Source dataset
uspto-grants-2015_08
Patent number
US09096558B2

Reaction notes

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