反应详情

To a suspension of 4-(4-methyl-piperazin-1-yl)-2-[(tetrahydro-pyran-4-yl)-(2,2,2-trifluoro-acetyl)-amino]-benzoic acid trifluoroacetate (2.16 g, 4.1 mmol) in dry dichloromethane (20 mL) were added oxalyl chloride (0.69 mL, 8.2 mmol) and N,N-dimethylformamide (1-2 drops). The mixture was stirred at room temperature for 1.5 hours then evaporated to dryness. The resulting crude acyl chloride was taken-up with toluene and evaporated again then dissolved in dry tetrahydrofuran (30 mL) and N,N-diisopropylethylamine (2.8 mL, 16.4 mmol) and treated with 5-(3,5-difluoro-benzenesulfonyl)-1-trityl-1H-indazol-3-ylamine (1.5 g, 2.72 mmol). The mixture was stirred at room temperature overnight then evaporated to dryness. The residue was dissolved in dichloromethane, washed with saturated solution of sodium hydrogenocarbonate and with brine, dried over sodium sulfate and evaporated to dryness. The crude was purified by flash chromatography on silica gel using dichloromethane/acetone 1:1 as the eluant, affording the title compound as a pale yellow solid (2.4 g, 93% yield).

1. customthen evaporated to dryness
2. customevaporated again
3. dissolutionthen dissolved in dry tetrahydrofuran (30 mL)
4. stirringThe mixture was stirred at room temperature overnight
5. customthen evaporated to dryness
6. dissolutionThe residue was dissolved in dichloromethane
7. washwashed with saturated solution of sodium hydrogenocarbonate and with brine
8. dry with materialdried over sodium sulfate
9. customevaporated to dryness
10. customThe crude was purified by flash chromatography on silica gel