反应详情

A solution of cis-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.100 g, 0.23 mmol) in pyridine (2.5 mL) was treated with 2,2-dimethyl-3-phenylpropanoyl chloride (0.120 g, 0.61 mmol). The reaction mixture was stirred for 2 h at room temperature under a nitrogen atmosphere. Saturated sodium bicarbonate solution (10 mL) was added, and the reaction mixture was stirred for 20 min. Solvent was removed under reduced pressure. Dichloromethane and saturated sodium bicarbonate solution was added to the residue. The layers were separated using an Empore extraction cartridge. The organic solvent was removed under reduced pressure. The crude compound was purified by flash chromatography on silica gel, using 10% methanol in dichloromethane as eluent to give 0.085 g (62%) cis-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2,2-dimethyl-3-phenylpropanamide. 1H NMR (CDCl3, 400 MHz) δ 8.595-8.574 (m, 1H), 8.372 (s, 1H), 7.985 (s, 1H), 7.292-7.158 (m, 7H), 4.923 (m, 1H), 3.891 (s, 3H), 3.050-3.013 (m, 1H), 2.965 (s, 2H), 2.65-2.55 (m, 5H), 2.440-2.346 (m, 4H), 2.244-2.166 (m, 4H), 1.854-1.823 (m, 3H), 1.688 (m, 3H), 1.334 (s, 6H); HPLC Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 5.517 min (100%).

1. stirringthe reaction mixture was stirred for 20 min
2. customSolvent was removed under reduced pressure
3. additionDichloromethane and saturated sodium bicarbonate solution was added to the residue
4. customThe layers were separated
5. extractionan Empore extraction cartridge
6. customThe organic solvent was removed under reduced pressure
7. customThe crude compound was purified by flash chromatography on silica gel