Dimethylformamide → methyl 3-formyl-1-methyl-1H-indazole-6-carboxylate
Reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([O:18][CH3:19])=[O:17])[CH:14]=2)[CH:9]=[N:8]1.[OH-].[Na+].CN([CH:25]=[O:26])C>>[CH:25]([C:9]1[C:10]2[C:15](=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[CH:12][CH:11]=2)[N:7]([CH3:6])[N:8]=1)=[O:26]Participants
5
Procedure
In a dry flask under nitrogen is added dry DMF (1.6 mL) and the solution cooled to −5C in an ice/ethanol bath. Phosphorous oxychloride (530 uL, 5.7 mmol) is added via syringe and the solution is allowed to stir for 30 minutes in the bath. Methyl 1-methyl-1H-indazole-6-carboxylate, (500 mg, 2.84 mmol, prepared as in Jadhav et al, U.S. Pat. No. 5,760,028) dissolved in DMF (3 mL) is added slowly to the cold solution. The reaction is then warmed to 35C, stirred for four hours, and then poured onto crushed ice. The resulting slurry is neutralized with 1N NaOH to pH=7, heated rapidly to boiling for 1 minute, cooled quickly to room temperature, and the solution extracted with ethyl acetate. The combined organics are washed with water and brine, dried, filtered and concentrated. The resulting oil is purified by flash chromatography to afford the product.