1,3,4-Thiadiazol-2-amine → N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amine

HRID 2283624Notes

Reaction equation

HRID 2283624 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[N:5][N:6]=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.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.Cl[Ti](OC(C)C)(OC(C)C)OC(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:3][CH:4]=[N:5][N:6]=1

Participants

6

Reactant 3

HCID 199091,3,4-Thiadiazol-2-amineHCID 691752,4-DimethoxybenzaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 58042278N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amineYield 8.6%

Reagents, catalysts & solvents 2

HCID 178460663HCID 178460663, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-amino-1,3,4-thiadiazole (3.05 g, 30.2 mmol) and 2,4-dimethoxy-benzaldehyde (4.55 g, 27.4 mmol) in dichloromethane (125 mL) was added chlorotriisopropoxytitanium (16 mL, 67 mmol) portionwise over 5 minutes. After stirring for 1 hour, sodium triacetoxyborohydride (11.72 g, 55.3 mmol) was added portion wise and stirred for 24 hours. The reaction was quenched with saturated aqueous sodium bicarbonate solution, adjusted to pH 9 with sodium hydroxide (6 N aqueous solution) and extracted with dichloromethane. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (0% to 10% methanol in dichloromethane gradient elution) to afford the title compound as a white solid (590 mg).

Workup

  1. stirringstirred for 24 hours
  2. customThe reaction was quenched with saturated aqueous sodium bicarbonate solution
  3. extractionextracted with dichloromethane
  4. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel flash column chromatography (0% to 10% methanol in dichloromethane gradient elution)

Sources & evidence

ORD record
ord-cf33007ab8a646b39ff6fff0101e2a27
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Reaction notes

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