Methyl 2-methylindazole-6-carboxylate

Methyl 2-methylindazole-6-carboxylate Property

Boiling point:

338.9±15.0 °C(Predicted)

Density 

1.23±0.1 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

form 

solid

pka

-0.39±0.30(Predicted)

Appearance

Off-white to light yellow Solid

Safety

WGK Germany 

3

HS Code 

2933998090

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

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

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

Methyl 2-methylindazole-6-carboxylate Chemical Properties,Usage,Production

Uses

2-Methyl-2H-indazole-6-carboxylic Acid Methyl Ester is a useful synthetic intermediate. It is an analog of Indazole-3-carboxylic Acid Methyl Ester (I505250) which has potential as application of N-benzoylindazole derivatives and analogues as inhibitors of human neutrophil elastase. Indazole-3-carboxylic Acid Methyl Ester (I505250) is also used in the preparation of indazole-pyridine based protain kinase/Akt inhibitors.

Synthesis

Sodium hydride (60% dispersed in mineral oil, 154 mg, 3.85 mmol) was added batchwise to an anhydrous tetrahydrofuran solution of methyl 1H-indazole-6-carboxylate (566 mg, 3.21 mmol) under cooling conditions in an ice bath. The reaction mixture was stirred at room temperature for 30 min. Subsequently, iodomethane (547 mg, 3.85 mmol) was slowly added dropwise and the reaction was continued with stirring at room temperature overnight. Upon completion of the reaction, the mixture was cooled to 0 °C, the reaction was quenched by careful addition of water and extracted with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography afforded methyl 1-methyl-1H-indazole-6-carboxylate (130 mg) and methyl 2-methyl-2H-indazole-6-carboxylate (230 mg) in 59% overall yield. The structures of the products were confirmed by 1H NMR: 1-methyl-1H-indazole-6-carboxylic acid methyl ester: 1H NMR (400 MHz, CDCl3) δ 3.97 (3H, s), 4.14 (3H, s), 7.74-7.82 (2H, m), 8.02 (1H, s), 8.17 (1H, d, J = 0.8 Hz). 2-methyl-2H-indazole- 6-carboxylic acid methyl ester: 1H NMR (400 MHz, CDCl3) δ 3.94 (3H, s), 4.25 (3H, s), 7.65-7.72 (2H, m), 7.92 (1H, s), 8.47 (1H, d, J = 1.2 Hz). Mass spectral analysis: [M + H]+ m/z 191.0815 (calculated value C10H11N2O2, 191.0816).

References

[1] Patent: WO2014/89364, 2014, A1. Location in patent: Paragraph 00477; 00478