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

HRID 46277

Reaction equation

HRID 46277 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 and Stark conditions for 2 hours. The reaction mixture was evaporated, the residue taken up in methanol (25 ml), NaBH4 (600 mg; 15.9 mmol) 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; ethyl acetate:heptane 25:75 to 60:40) to furnish a semi-solid residue that was re-evaporated from heptane. 2-3 ml tBuOMe was added, then 2-3 ml heptane, the solid filtered off, washed with heptane and dried to afford 1.22 g of the title compound.

Workup

  1. temperaturewas refluxed under Dean and 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; ethyl acetate:heptane 25:75 to 60:40)
  12. customto furnish a semi-solid residue that
  13. customwas re-evaporated from heptane
  14. addition2-3 ml tBuOMe was added
  15. filtration2-3 ml heptane, the solid filtered off
  16. washwashed with heptane
  17. customdried

Sources & evidence

ORD record
ord-9c81c6d07ee147a8959a5a43f477a3e1
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Linked notes

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