Chemical Properties
Off White Solid
Uses
Granisetron Impurity D.
Uses
1-Methylindazole-3-carboxylic acid is used as important raw material and intermediate used in organic Synthesis, pharmaceuticals, agrochemicals and dyestuff. It is also used as a pharmaceutical adjuvant, Granisetron Impurity D.
Synthesis Reference(s)
The Journal of Organic Chemistry, 63, p. 8448, 1998
DOI: 10.1021/jo981557o
Synthesis
Calcium oxide (7.0 g, 0.124 mol, 2.0 molar equiv.) was added to technical methanol (150 ml), and the mixture was heated under reflux for 2 hours in a nitrogen atmosphere Indazole-3-carboxylic acid (10 g, 0.062 mol) was then added, and the reflux was continued for 2 hours. Dimethyl sulfate (15.6 g, 11.8 ml, 0.124 mole, 2.0 molar equiv.) was added dropwise under reflux for 2 hours, and the reflux continued for 2 hours. Water (100 ml) and 46% aqueous sodium hydroxide solution were added to produce a pH of about 14. Then, conc. hydrochloric acid was added to the reaction mixture to produce a pH of about 4. Calcium sulfate was collected by filtration and washed on a filter with hot methanol (3×30 ml). The methanol was removed under reduced pressure from the filtrate. The residuary mixture was stirred vigorously for 6 hours with a controlled pH of about 4. The solid product was collected by filtration, washed with water (3×30 ml), and dried in an oven at 50° C. overnight to give crude 1-Methylindazole-3-carboxylic acid.
Purification Methods
The crude 1-Methylindazole-3-carboxylic acid (1-MICA) (10.4 g) was treated by slurry in a methanol-water (3:7) mixture heated under reflux for 4 hours. The suspension was cooled to room temperature, and the solid product was collected by filtration, washed with the methanol-water (3:7) mixture (3×10 ml), and dried in an oven at 50° C. overnight to give pure 1-MICA (9.3 g, 85.6% yield, purity by HPLC: 99.70%).
