1H-indazole-6-carboxylic acid Chemical Properties

Melting point:

302-307 °C

Boiling point:

443.7±18.0 °C(Predicted)

Density 

1.506±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

4.01±0.30(Predicted)

form 

Crystalline Powder

color 

White to light brown

InChI

InChI=1S/C8H6N2O2/c11-8(12)5-1-2-6-4-9-10-7(6)3-5/h1-4H,(H,9,10)(H,11,12)

InChIKey

DNCVTVVLMRHJCJ-UHFFFAOYSA-N

SMILES

N1C2=C(C=CC(C(O)=O)=C2)C=N1

Safety Information

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

29339980

1H-indazole-6-carboxylic acid Usage And Synthesis

Uses

1H-Indazole-6-carboxylic Acid is used as a reagent to synthesize azabicyclic aryl amides, which act as α7 nicotinic acetylcholine receptor agonists.

Preparation

Synthesis of 1H-indazole-6-carboxylic acid, H2L3: MeL3Ac (1.0 g; 4.6 mmol) was dissolved in 40 mL THF, and this solution was added to a 40 mL aqueous solution of lithium hydroxide (5.0 g; 210 mmol). The resulting suspension was heated at reflux with vigorous stirring overnight, after which time the solution was concentrated under vacuum to remove the organic phase. The resulting solution was filtered, adjusted to pH 3 with conc. HCl, to precipitate the product as a pale brown solid, which was filtered, washed with water and dried under vacuum. Yield 315 mg, 43%. mp 292–296 °C (decomp);
δH (500 MHz, d6-DMSO): 7.67 (dd, 1H, J = 8.3, 1.0 Hz, H4 ), 7.85 (dd, 1H, J = 8.3, 0.8 Hz, H3 ), 8.15 (s, 1H, H6 ), 8.18 (d, 1H, J = 0.8 Hz, H2 ), 13.24 (br s, 2H, H1 & H5 ); δC (125 MHz, CD3OD): 114.1, 122.0, 122.6, 127.1, 130.6, 135.2, 141.4, 170.4; HRMS-ESI m/z: found: 163.0503; C8H7N2O2 requires: 163.0502 [M + H+ ]; ˉνmax/cm?1 (KBr): 3258 br, 2864 br, 2582 br, 1679 s, 1579 m, 1518 m, 1425 m, 1230 s, 1087 m, 954 s, 857 m, 762 m, 693 m.

Synthesis

General procedure for the synthesis of 1H-indazole-6-carboxylic acid from methyl 1H-indazole-6-carboxylate: to a stirred solution of methyl 1H-indazole-6-carboxylate (1.0 g, 5.676 mmol, 1 eq.) in a solvent mixture of tetrahydrofuran/ethanol/water (1:1:1, 10 mL) was added lithium hydroxide (476 mg, 11.353 mmol, 2 eq.) . The reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, the solvent was removed by evaporation and the residue was diluted with 10 mL of water and the pH was adjusted to 4-5 with 2N hydrochloric acid to give a solid precipitate. The precipitate was collected by filtration and dried to give 1H-indazole-6-carboxylic acid (900 mg, 97% yield) as an off-white solid.TLC conditions: methanol/dichloromethane (1:9), Rf value 0.1.1H NMR (300 MHz, DMSO-d6): δ 13.36 (s, 1H), 13.04 (s, 1H), 8.24-8.08 (m , 2H), 7.85 (dd, J=8.5,0.9Hz, 1H), 7.67 (dd, J=8.4,1.3Hz, 1H).

References

[1] Patent: WO2016/8590, 2016, A1. Location in patent: Page/Page column 56
[2] Patent: WO2005/44817, 2005, A1. Location in patent: Page/Page column 118-119
[3] Patent: CN105693520, 2016, A. Location in patent: Paragraph 0196; 0197; 0198; 0199; 0200; 0201
[4] Patent: EP3067351, 2016, A1. Location in patent: Paragraph 0087; 0088

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