Diisopropylethylamine → 5-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine

HRID 2402603Notes

Reaction equation

HRID 2402603 reaction equation
Cl.NO.C([N:7](CC)C(C)C)(C)C.[Br:13][C:14]1[N:19]=[C:18]([NH:20][C:21]([NH:23]C(OCC)=O)=S)[CH:17]=[CH:16][CH:15]=1>CCO.CO>[Br:13][C:14]1[N:19]2[N:7]=[C:21]([NH2:23])[N:20]=[C:18]2[CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 443297Hydroxyamine hydrochlorideHCID 57361094Ethyl (6-bromo-pyridin-2-ylamino)carbonothioylcarbamate

Product 1

HCID 252159395-Bromo-[1,2,4]triazolo[1,5-a]pyridin-2-amine

Reagents, catalysts & solvents 1

HCID 18681192Ethanol, mixt. with methanolSolvent

Conditions

Temperature
20 °C

Procedure

To a suspension of hydroxylamine hydrochloride (101.8 g, 1.465 mol) in EtOH/MeOH (1:1, 900 mL) is added N,N-diisopropylethylamine (145.3 mL, 0.879 mol) and the mixture is stirred at room temp. (20° C.) for 1 h. 1-(6-Bromo-pyridin-2-yl)-3-carboethoxy-thiourea (2) (89.0 g, 0.293 mol) is then added and the mixture slowly heated to reflux (Note: bleach scrubber is required to quench H2S evolved). After 3 h at reflux, the mixture is allowed to cool and filtered to collect the precipitated solid. Further product is collected by evaporation in vacuo of the filtrate, addition of H2O (250 mL) and filtration. The combined solids are washed successively with H2O (250 mL), EtOH/MeOH (1:1, 250 mL) and Et2O (250 mL) then dried in vacuo to afford the triazolopyridine derivative (3) as a solid. The compound may be used as such for the next step without any purification. 1H (400 MHz, DMSO-d6) δ 7.43-7.34 (2H, m, 2×aromatic-H), 7.24 (1H, dd, J 6.8 and 1.8 Hz, aromatic-H), 6.30 (2H, br, NH2); m/z 213/215 (1:1, M+H+, 100%).

Workup

  1. temperaturethe mixture slowly heated
  2. temperatureto reflux
  3. custom(Note: bleach scrubber is required to quench H2S evolved)
  4. temperatureAfter 3 h at reflux
  5. temperatureto cool
  6. filtrationfiltered
  7. customto collect the precipitated solid
  8. filtrationFurther product is collected by evaporation in vacuo of the filtrate, addition of H2O (250 mL) and filtration
  9. washThe combined solids are washed successively with H2O (250 mL), EtOH/MeOH (1:1, 250 mL) and Et2O (250 mL)
  10. customthen dried in vacuo

Sources & evidence

ORD record
ord-7ab6c77a4909490e957f2e89490492bd
Source dataset
uspto-grants-2014_08
Patent number
US08796457B2

Reaction notes

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