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

HRID 885642Notes

Reaction equation

HRID 885642 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) may then be 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 may be 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 may be 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-1d9b261375c24ff1af232593db497113
Source dataset
uspto-grants-2012_08
Patent number
US08242274B2

Reaction notes

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