ChemicalBook CAS DataBase List 1-Methylindazole-3-carboxylic acid

1-Methylindazole-3-carboxylic acid synthesis

9synthesis methods

Product Name:1-Methylindazole-3-carboxylic acid
CAS Number:50890-83-0
Molecular formula:C9H8N2O2
Molecular Weight:176.17

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.

512-56-1 Synthesis

512-56-1
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4498-67-3 Synthesis

4498-67-3
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50890-83-0
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$10.00/1g

Yield:50890-83-0 78.3%

Reaction Conditions:

Stage #1:1H-Indazole-3-carboxylic acid with magnesium ethylate in propan-1-ol for 2 h;Heating / reflux;
Stage #2:trimethyl phosphite in propan-1-ol at 20; for 7 h;Heating / reflux;

Steps:

6 Example 6; Preparation of 1-MICA by reaction of ICA with trimethyl phosphate in 1-propanol in the presence of magnesium ethoxide
Magnesium ethoxide (14.10 g, 0.124 mole, 2 molar equiv.) was added to technical 1-propanol (100 ml) under nitrogen atmosphere and the mixture was heated under reflux for 2 hour. Indazole-3-carboxylic acid (10 g, 0.0617 mole) was then added and the reflux was continued for 2 hours. Trimethyl phosphate (14:7 g, 12.3 ml, 0.105 mole, 1.7 molar equiv.) was added dropwise under reflux for 2 hours and the reflux was continued for a further 5 hours (the composition of the reaction mixture by HPLC was: 95.61% 1-MICA, 1.89% 2-MICA, and 2.50% ICA). The mixture was kept at room temperature overnight (the composition of the reaction mixture by HPLC was: 97.24% 1-MICA, 2.17% 2-MICA, and 0.58% ICA). Water (100 ml) and 46% aqueous sodium hydroxide solution were added to the reaction mixture to produce pH of about 14. Then, conc. hydrochloric acid was added to the suspension to produce pH of about 4 and obtain a solution. The propanol was removed under reduced pressure from the solution. The residuary mixture was stirred vigorously for 6 hours with a control of the pH of about 4. The solid product was collected by filtration, washed with water (3 x 30 ml), and dried in oven at 50°C overnight to give crude 1-MICA (10.1 g, 93.0% yield, purity by HPLC: 99.24%). The crude 1-MICA (10.1 g) was treated by slurry in methanol-water (3:7) mixture (31 ml) at heating under reflux for 4 hours. The solid product was collected by filtration, washed with methanol-water (3:7) mixture (3 × 10 ml), and dried in oven at 50°C to obtain pure 1-MICA (8.5 g, 78.3% yield, purity by HPLC: 99.78%).

References:

Chemagis Ltd. EP1484321, 2004, A1 Location in patent:Page 8-9

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4498-67-3 Synthesis

4498-67-3
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$6.00/5g