反应详情

To a solution of cis-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (75 mg, 0.17 mmol) and triethylamine (34 mg, 0.34 mmol) in dichloromethane (2.5 ml) was added hydrocinnamoyl chloride (34 mg, 0.20 mmol) in dichloromethane (0.5 ml) dropwise. The solution was stirred at room temperature for 48 hr and a further equivalent of hydrocinnamoyl chloride was then added. The reaction mixture was stirred for a further 24 hr. The resulting mixture was partitioned between dichloromethane (4 ml) and 2N NaOH (1.5 ml) and passed through an Empore extraction cartridge. Evaporation of the solvent gave an oily solid which was purified by silica gel chromatography using 10-20% MeOH/dichloromethane to give cis-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-3-phenylpropanamide (12 mg, 13%). 1H NMR (CDCl3): δH 8.55 (1H, d), 8.36 (1H, s), 7.75 (1H, s), 7.25 (7H, m), 5.51 (2H, bs), 4.91 (1H, m), 3.92 (3H, s), 3.09 (2H, m), 2.76 (2H, m), 2.34-2.59 (9H, m), 2.29 (3H, s), 2.16 (2H, m), 1.85 (4H, m), 1.66 (2H, m). LCMS (Micromass-Column: Pecosphere, C18, 3 um, 33×4.6 mm. Eluents: 0% B/A to 100% B/A in 4.5 min.(B: acetonitrile, A: 50 mM ammonia acetate buffer, PH 4.5), 3.5 mL/min.) Rt=1.92 mins, MH+=569.6.

1. stirringThe reaction mixture was stirred for a further 24 hr
2. customThe resulting mixture was partitioned between dichloromethane (4 ml) and 2N NaOH (1.5 ml)
3. extractionpassed through an Empore extraction cartridge
4. customEvaporation of the solvent
5. customgave an oily solid which
6. customwas purified by silica gel chromatography