3,5-DIBROMO-1-METHYL-1H-1,2,4-TRIAZOLE

3,5-DIBROMO-1-METHYL-1H-1,2,4-TRIAZOLE Property

Boiling point:

326.6±25.0 °C(Predicted)

Density 

2.49±0.1 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

pka

-1.31±0.10(Predicted)

Appearance

White to off-white Solid

InChI

InChI=1S/C3H3Br2N3/c1-8-3(5)6-2(4)7-8/h1H3

InChIKey

OAPQSGTTZLYWJB-UHFFFAOYSA-N

SMILES

N1(C)C(Br)=NC(Br)=N1

Safety

HazardClass 

IRRITANT

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P321Specific treatment (see … on this label).

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

P501Dispose of contents/container to..…

3,5-DIBROMO-1-METHYL-1H-1,2,4-TRIAZOLE Chemical Properties,Usage,Production

Uses

3,5-Dibromo-1-methyl-1H-1,2,4-triazole is an intermediate in the preparation of modulators of Rho-associated protein kinase.

Synthesis

In a 250 mL round-bottomed flask, 3,5-dibromo-1H-1,2,4-triazole (8.00 g, 35.3 mmol) was dissolved in N,N-dimethylformamide (DMF, 80 mL) and the solution was cooled to 0-5°C (ice bath). Sodium hydride (60% mineral oil dispersion, 1.69 g, 42.3 mmol) was added in batches and the reaction mixture was stirred at 0-5°C for 45 min, followed by 15 min at room temperature. Iodomethane (10.0 g, 4.41 mL, 70.5 mmol) was slowly added dropwise at 0-5°C (ice bath). After completion of the dropwise addition, the reaction mixture was stirred at room temperature for 18 hours. After completion of the reaction, the mixture was concentrated under reduced pressure and the residue was diluted with ethyl acetate (200 mL) and water (200 mL), the aqueous phase was separated and extracted with ethyl acetate (2 x 200 mL). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford 3,5-dibromo-1-methyl-1,2,4-triazole as a light yellow solid (8.15 g, 96% yield). The product was characterized by 1H NMR (CDCl3, 300 MHz): δ 3.89 (s, 3H). Mass spectrum (ES+) m/z: 240.0, 242.0, 244.0 [M + H, 2 Br isotope].

References

[1] Patent: WO2018/87018, 2018, A1. Location in patent: Page/Page column 55
[2] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 13, p. 2679 - 2685
[3] Patent: WO2014/195321, 2014, A1. Location in patent: Page/Page column 16; 17
[4] Patent: WO2014/195322, 2014, A1. Location in patent: Page/Page column 16
[5] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 24, p. 5805 - 5813