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

HRID 509109Notes

Reaction equation

HRID 509109 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 86%

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-dimethoxybenzaldehyde (4.55 g, 27.4 mmol) in dichloromethane (125 mL) was added chlorotriisopropoxytitanium (16 mL, 67.0 mmol) portion-wise 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 aqueous sodium hydroxide (6 N 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 (0-10% methanol in dichloromethane gradient elution) to afford the title compound as a white solid (0.590 g, 86%).

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 (0-10% methanol in dichloromethane gradient elution)

Sources & evidence

ORD record
ord-e6d66607b6134cc0949909cbc604856e
Source dataset
uspto-grants-2015_08
Patent number
US09096558B2

Reaction notes

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