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

HRID 1619631Notes

Reaction equation

HRID 1619631 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:4]=1[CH:5]=O.[NH2:13][C:14]1[S:15][CH:16]=[N:17][N:18]=1.[BH4-].[Na+].C(=O)(O)[O-].[Na+]>C1(C)C(C)=CC=CC=1.CC1CCCO1.O.CO>[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:4]=1[CH2:5][NH:13][C:14]1[S:15][CH:16]=[N:17][N:18]=1

Participants

9

Reactant 4

HCID 199091,3,4-Thiadiazol-2-amineHCID 691752,4-DimethoxybenzaldehydeHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydride

Product 1

HCID 58042278N-(2,4-dimethoxybenzyl)-1,3,4-thiadiazol-2-amineYield 73.5%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 7237O-XyleneSolventHCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
5 °C

Procedure

2,4-Dimethoxybenzaldehyde (771 g, 4.64 mol) was added to a suspension of 2-amino-1,3,4-thiadiazole (391.2 g, 3.87 mol) in xylene (5.87 L) and heated to reflux for 18 hours. Dean-Stark apparatus was used to remove the water. The reaction mixture was cooled to 5° C. and diluted with 2-methyltetrahydrofuran (2.93 L). Sodium tetrahydroborate (73.17 g, 1.93 mol) was added as a single portion. Methanol (782.8 mL) was then added slowly over 30 minutes, maintaining the temperature below 15° C. After a further 30 minutes, water (1 L) was added followed by saturated aqueous sodium bicarbonate solution (1 L) and the mixture stirred at ambient temperature for 18 hours. The biphasic mixture was diluted with 2-methyltetrahydrofuran and heated to 43° C. to aid dissolution. The layers were separated and the organic layer washed with water (3 L) before concentrating in vacuo. The resulting solid was slurried in heptanes (2.5 L), homogenised, filtered, washed with tert-butylmethyl ether and dried to afford the title compound (715 g).

Workup

  1. temperatureheated
  2. temperatureto reflux for 18 hours
  3. customto remove the water
  4. additiondiluted with 2-methyltetrahydrofuran (2.93 L)
  5. temperaturemaintaining the temperature below 15° C
  6. temperatureheated to 43° C.
  7. dissolutiondissolution
  8. customThe layers were separated
  9. washthe organic layer washed with water (3 L)
  10. concentrationbefore concentrating in vacuo
  11. stirringhomogenised
  12. filtrationfiltered
  13. washwashed with tert-butylmethyl ether
  14. customdried

Sources & evidence

ORD record
ord-193b47ba10ac44109e66e3b051708d29
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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