5-Chloromethyl-2H-1,2,4-triazolin-3-one Chemical Properties

Melting point:

199°C(lit.)

Density 

1.83±0.1 g/cm3(Predicted)

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

solubility 

soluble in Methanol

form 

powder to crystal

pka

7.46±0.20(Predicted)

color 

White to Almost white

InChI

InChI=1S/C3H4ClN3O/c4-1-2-5-3(8)7-6-2/h1H2,(H2,5,6,7,8)

InChIKey

ZLRBJVJEQXBAAI-UHFFFAOYSA-N

SMILES

N1C(CCl)=NC(=O)N1

CAS DataBase Reference

252742-72-6

Safety Information

RIDADR 

UN 3261 8/PG II

HazardClass 

8

PackingGroup 

II

HS Code 

2914390090

5-Chloromethyl-2H-1,2,4-triazolin-3-one Usage And Synthesis

Chemical Properties

White to Almost white powder to crystal

Uses

5-Chloromethyl-2H-1,2,4-triazolin-3-one is an intermediate used in the synthesis of Aprepitant (A729800) and Fosaprepitant, used as antiemetic drugs.

Application

3-Chloromethyl-1,2,4-triazolin-5-one is an intermediate in organic synthesis and pharmaceutical intermediate, which can be used in laboratory R&D synthesis process and chemical biological R&D process.

Hazard

5-Chloromethyl-2H-1,2,4-triazolin-3-one is a hazardous chemical that is corrosive to metals, irritating to the eyes and skin, and may cause respiratory irritation.

Synthesis

4.0 g of aminourea hydrochloride, 9.67 mL of 2-chloro-1,1,1-trimethoxyethane and 40 mL of methanol were mixed in a reaction vial and the reaction was stirred at room temperature for 3 days. Subsequently, 3.5 mL of 2-chloro-1,1,1-trimethoxyethane was added to the reaction system to ensure complete reaction. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure to remove the solvent. The concentrated crude product was extracted by partitioning between ethyl acetate and 1N hydrochloric acid solution. The organic phase was separated and washed twice with 1N hydrochloric acid solution. All aqueous phase extracts were combined and then extracted five times with ethyl acetate. All organic phases were combined, dried over anhydrous sodium sulfate, filtered to remove the desiccant and the filtrate was concentrated under reduced pressure. The resulting solid was ground with ethyl acetate to give 5-chloromethyl-2,4-dihydro[1,2,4]triazol-3-one, and the product could be used in subsequent reactions without further purification. Yield: 2.97 g (62% yield). The product was characterized by 1H NMR (500 MHz, DMSO-d6): δ 4.49 (2H, s), 11.55 (1H, br.s), 11.70 (1H, br.s).

References

[1] Tetrahedron Letters, 2000, vol. 41, # 44, p. 8661 - 8664
[2] Patent: US2012/28939, 2012, A1. Location in patent: Page/Page column 27
[3] Patent: WO2011/92128, 2011, A1. Location in patent: Page/Page column 51-52
[4] Patent: WO2014/139328, 2014, A1. Location in patent: Page/Page column 614
[5] Patent: WO2006/133426, 2006, A2. Location in patent: Page/Page column 276

5-Chloromethyl-2H-1,2,4-triazolin-3-one(252742-72-6)Related Product Information

• Caprolactam
• Aprepitant
• Acetaminophen
• Rivaroxaban
• 5-Chloromethyl-2H-1,2,4-triazolin-3-one