反应详情

To chilled tetrahydrofuran (600 mL) at −78° C., under Argon, was added 200 mL of a 1.7M solution of tert-butyllithium in n-pentane. After 15 minutes at −78° C., a solution of 22.4 g (106.13 mmol) 5-bromo-3-methyl-1H-indazole (commercially available, or see WO 2006/081230, 68-69) in 300 mL tetrahydrofuran was added dropwise at such a rate that the temperature of the solution did not exceed −70° C. The mixture was stirred for 30 minutes before 24.5 mL N,N-dimethylformamide was added dropwise. After 20 minutes the cooling bath was removed and stirring continued for 1 hour before 41 mL water was added carefully. A further 201 mL water was added and the mixture was extracted with ethyl acetate. The organic extract was washed with saturated sodium chloride solution and dried over sodium sulfate. The solvents were distilled off to give 18.5 g crude 3-methyl-1H-indazole-5-carbaldehyde, which was used without purification. 1H-NMR (DMSO-d6): δ=13.13 (br s, 1H), 10.01 (s, 1H), 8.40 (s, 1H), 7.81 (d, 1H), 7.58 (d, 1H), 2.56 (s, 3H) ppm. MS (ES+): 161.34 (M++1, 100%).

1. additionwas added dropwise at such a rate that the temperature of the solution
2. customdid not exceed −70° C
3. additionwas added dropwise
4. customAfter 20 minutes the cooling bath was removed
5. waitcontinued for 1 hour before 41 mL water
6. additionwas added carefully
7. additionA further 201 mL water was added
8. extractionthe mixture was extracted with ethyl acetate
9. extractionThe organic extract
10. washwas washed with saturated sodium chloride solution
11. dry with materialdried over sodium sulfate
12. distillationThe solvents were distilled off