反应详情

6.31 g (56.2 mmol) of potassium tert-butoxide are added to a solution of 8.39 g (23.4 mmol) of 2-amino-6-(benzylthio)-4-(4-hydroxyphenyl)pyridine-3,5-dicarbonitrile [preparation according to WO 01/25210, Example A 383, from 2-amino-4-(4-hydroxyphenyl)-6-mercaptopyridine-3,5-dicarbonitrile and benzyl bromide] in 105.5 ml of ethanol. The mixture is stirred at RT for 1 h, and 4.05 g (28.1 mmol) of 2-dimethylaminoethyl chloride hydrochloride are then added. The mixture is then stirred at +78° C. for 3 h. After cooling, the reaction mixture is filtered and the filtrate is concentrated using a rotary evaporator. The residue is purified directly by preparative HPLC (column: Merck 210 g RP silica gel Gromsil 1200DS-4 HR 10 μm, 50 mm×200 mm; mobile phase A=water+0.1% formic acid, mobile phase B=acetonitrile; gradient: 0 min 10% B→5 min 10% B→6 min 90% B→22 min 90% B→22 min 10% B→28 min 10% B; flow rate: 110 ml/min; wavelength: 220 nm).

1. stirringThe mixture is then stirred at +78° C. for 3 h
2. temperatureAfter cooling
3. filtrationthe reaction mixture is filtered
4. concentrationthe filtrate is concentrated
5. customa rotary evaporator
6. customThe residue is purified directly by preparative HPLC (column: Merck 210 g RP silica gel Gromsil 1200DS-4 HR 10 μm, 50 mm×200 mm; mobile phase A=water+0.1% formic acid, mobile phase B=acetonitrile; gradient: 0 min 10% B→5 min 10% B→6 min 90% B→22 min 90% B→22 min 10% B→28 min 10% B; flow rate: 110 ml/min; wavelength: 220 nm)