反应详情

A 30 ml round-bottomed flask equipped with a magnetic stirrer and with a septum having a top-mounted argon intake is charged with 272 mg of 5-(2,6-difluorophenyl)-3-{[1-(trifluoromethanesulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carbonitrile, 10 ml of ethanol, 5 ml of THF and 0.611 ml of 9.3N NaOH. After 2 h of reflux, the mixture is cooled, and 50 ml of a 1M aqueous solution of potassium dihydrogen phosphate are poured in. The product is extracted with AcOEt, washed with saturated aqueous NaCl solution, dried over MgSO4, filtered and concentrated to dryness under RP. The crude solid obtained is dissolved in 4 ml of DMF and than 275 mg of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluoride (BOP), 84 mg of 1-hydroxybenzotriazole (HOBT), 44 mg of ammonium chloride and 2 ml of N,N-diisopropylethylamine (DIPEA) are added. After 3 h at RT, the mixture is poured into water, extracted with AcOEt, and washed with saturated aqueous NaCl solution. Drying of MgSO4, filtering and concentration under RP give 300 mg of 5-(2,6-difluorophenyl)-3-{[1-(trifluoromethanesulphonyl)piperidin-4-yl]amino}-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrazolo[4,3-c]isoquinoline-7-carboxamide. MS (E/I): m/z=684 (M+).

1. customA 30 ml round-bottomed flask equipped with a magnetic stirrer and with a septum
2. temperatureAfter 2 h of reflux
3. temperaturethe mixture is cooled
4. extractionThe product is extracted with AcOEt
5. washwashed with saturated aqueous NaCl solution
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated to dryness under RP
9. customThe crude solid obtained
10. additionare added
11. extractionextracted with AcOEt
12. washwashed with saturated aqueous NaCl solution
13. dry with materialDrying of MgSO4
14. filtrationfiltering
15. concentrationconcentration under RP