3-(HYDROXYMETHYL)INDAZOLE

3-(HYDROXYMETHYL)INDAZOLE Property

Melting point:

138-139 °C

Boiling point:

380.3±17.0 °C(Predicted)

Density 

1.360±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

form 

solid

pka

13.56±0.10(Predicted)

color 

White

Safety

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.

3-(HYDROXYMETHYL)INDAZOLE Chemical Properties,Usage,Production

Synthesis

The general procedure for the synthesis of 3-hydroxymethylindazole from indazole-3-carboxylic acid is as follows: 1. Synthesis of (1H-indazol-3-yl)methanol [Compound (I)]: indazole-3-carboxylic acid (500 mg, 3.08 mmol) was dissolved in tetrahydrofuran (THF, 10 mL) and sodium bis(2-methoxyethoxy)aluminum hydride (70% toluene solution, 1.78 g, 6.17 mmol) was added. It was cooled in an ice bath under argon protection and subsequently heated and stirred at reflux for 2 hours. 2. Cooled in an ice bath again, added sodium bis(2-methoxyethoxy)aluminum hydride (70% toluene solution, 2.67 g, 9.25 mmol) to the reaction mixture and continued to heat and reflux for 2 hours. 3. After completion of the reaction, the ice bath was cooled, 2 mol/L sodium hydroxide solution (10 mL) was added and stirred for 15 minutes at room temperature. 4. The organic layer was separated and the aqueous layer was extracted with THF (5 mL × 3). Combine the organic layers and wash with saturated brine. 5. The aqueous layer was then extracted with ethyl acetate (5 mL × 2), all organic layers were combined, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure. 6. The residue was recrystallized with toluene/THF (10:1, 5 mL), the precipitated crystals were collected by filtration and washed with toluene/THF (10:1, 1 mL). 7. The resulting crystals were dried under pressure to give compound (I) (349 mg, 2.36 mmol, 77% yield). Characterization data: 1H-NMR (DMSO-d6, ppm): δ 4.80 (2H, d, J = 5.5 Hz), 5.19 (1H, br), 7.09 (1H, t, J ≈ 8 Hz), 7.33 (1H, t, J ≈ 8 Hz), 7.48 (1H, d, J = 8.4 Hz), 7.85 (1H, d, J = 8.4 Hz). 13C-NMR (DMSO-d6, ppm): δ 56.7, 109.9, 119.6, 120.5, 121.4, 125.8, 140.9, 145.5. Mass Spectrometry (C8H9N2O): Calculated [M + H]+: 149.0715, measured: 149.0710 (error: -0.5 mDa). Melting point: 142-143°C.

References

[1] Patent: EP1878737, 2008, A1. Location in patent: Page/Page column 12
[2] Patent: WO2005/9958, 2005, A1. Location in patent: Page 100-101
[3] Patent: US2006/142247, 2006, A1. Location in patent: Page/Page column 28
[4] Angewandte Chemie - International Edition, 2014, vol. 53, # 28, p. 7259 - 7263
[5] Angew. Chem., 2014, vol. 126, # 28, p. 7387 - 7391,5