反应详情

温度

105 °C

A mixture of 200 mg (1.25 mmol) 3-methyl-1H-indazole-5-carbaldehyde (Example 1A), 217 mg (1.50 mmol) 3-oxo-3-phenylpropanenitrile and 147 mg (1.25 mmol) 3-amino-4,4-difluorobut-2-enenitrile [obtainable by Thorpe reaction of acetonitrile with 2,2-difluoroacetonitrile, cf. Org. React. 15, 1 (1967), ibid. 31, 1 (1984)] in 1-pentanol (1.2 ml) containing powdered 4 Å molecular sieve was heated to 105° C. overnight. After cooling, the reaction mixture was diluted with acetonitrile and directly purified by preparative RP-HPLC (acetonitrile/water+0.1% TFA gradient) followed by chromatography on silica gel (eluent: toluene/dichloromethane/methanol 10:5:1 v/v) to afford 93 mg (19% of th.) of the racemic title compound.

1. additioncontaining
2. temperatureAfter cooling
3. customdirectly purified by preparative RP-HPLC (acetonitrile/water+0.1% TFA gradient)