反应详情

温度

130 °C

A solution of 150 mg (0.936 mmol) 3-methyl-1H-indazole-5-carbaldehyde (Example 1A) in n-pentanol (4 ml) containing powdered 4 Å molecular sieve was treated with 128 mg (0.936 mmol) 4,4,4-trifluoro-3-oxobutanenitrile (Example 8A) and stirred at 130° C. for 1 h. Then, 94 mg (0.44 mmol) 3-amino-3-[6-(trifluoromethyl)pyridin-2-yl]prop-2-enenitrile (Example 7A) and acetic acid (1.2 ml) were added, and the mixture was stirred at 130° C. for further 15 min. Upon cooling, water (6 ml) was added, the mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (30 ml), and the solution was washed several times with brine, then with water, dried over sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in THF (1 ml) containing 4 Å molecular sieve. A solution of tetra-n-butylammonium fluoride (TBAF, 1 N in THF, 1.5 ml) was added, and the mixture was stirred at 70° C. for 5 h. Upon cooling, the mixture was concentrated under reduced pressure, and the crude product was finally purified by preparative RP-HPLC (methanol/water+0.1% TFA gradient) to yield 15 mg (7% of th.) of the racemic title compound.

1. stirringthe mixture was stirred at 130° C. for further 15 min
2. temperatureUpon cooling
3. filtrationthe mixture was filtered
4. concentrationthe filtrate was concentrated under reduced pressure
5. dissolutionThe residue was dissolved in ethyl acetate (30 ml)
6. washthe solution was washed several times with brine
7. dry with materialwith water, dried over sodium sulfate
8. concentrationconcentrated under reduced pressure
9. dissolutionThe residue was dissolved in THF (1 ml)
10. additioncontaining 4 Å molecular sieve
11. additionA solution of tetra-n-butylammonium fluoride (TBAF, 1 N in THF, 1.5 ml) was added
12. stirringthe mixture was stirred at 70° C. for 5 h
13. temperatureUpon cooling
14. concentrationthe mixture was concentrated under reduced pressure
15. customthe crude product was finally purified by preparative RP-HPLC (methanol/water+0.1% TFA gradient)