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

HRID 2283660Notes

Reaction equation

HRID 2283660 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.CCCCCCC.C(OC)(C)(C)C>[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

9

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 3

HCID 1140TolueneSolventHCID 8900HeptaneSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

A mixture of 5-amino-1,2,4-thiadiazole (1.00 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 concentrated in vacuo, and the resulting 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 overnight at ambient temperature. An 2M aqueous solution of hydrogen chloride (1 mL) was added followed by a 2M aqueous solution of sodium hydroxide (10 mL). The mixture was concentrated in vacuo, water (20 mL) added and the mixture extracted with ethyl acetate (2×30 mL). The combined organics were washed with brine (20 mL), dried, and concentrated in vacuo. The residue was purified by silica gel column chromatography (ISCO™ column, 25% to 60% ethyl acetate in heptane gradient elution) to furnish a semi-solid residue. 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. concentrationThe reaction mixture was concentrated in vacuo
  3. additionafter each addition) and the reaction
  4. waitwas left
  5. concentrationThe mixture was concentrated in vacuo, water (20 mL)
  6. additionadded
  7. extractionthe mixture extracted with ethyl acetate (2×30 mL)
  8. washThe combined organics were washed with brine (20 mL)
  9. customdried
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by silica gel column chromatography (ISCO™ column, 25% to 60% ethyl acetate in heptane gradient elution)
  12. customto furnish a semi-solid residue
  13. filtrationThe resulting solid was collected by filtration
  14. washwashed with heptane
  15. customdried

Sources & evidence

ORD record
ord-4dca276df28548e18a4f4e36230a72e4
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Reaction notes

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