反应详情

温度

90 °C

A mixture of (S)-1-[1-(cis-3-benzyloxycyclobutyl)-6-fluoro-1H-benzoimidazol-2-yl]ethylamine (310 mg, 0.91 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (219 mg, 0.91 mmol) and DIPEA (0.81 mL, 4.57 mmol) in IPA (5 mL) was heated at 90° C. in a sealed vial for 16 h. After cooling to RT, the reaction mixture was concentrated in vacuo, dissolved in DCM and loaded onto an Isolute® SCX-2 cartridge which was washed with DCM, MeOH followed by 2M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) to afford the title compound as a glassy white solid (320 mg, 76%). LCMS (Method B): RT 2.76 min [M+H]+ 458. 1H NMR (CDCl3, 400 MHz): δ 8.48 (1H, s), 7.95 (1H, s), 7.71-7.58 (2H, m), 7.42-7.35 (5H, m), 7.07-6.90 (2H, m), 5.95 (1H, s, br), 4.97-4.80 (m, 1H), 4.52 (2H, s), 4.05-3.92 (1H, m), 3.01-2.86 (2H, m), 2.81-2.64 (1H, m), 1.75 (3H, d, J=6.85 Hz).

1. temperatureAfter cooling to RT
2. concentrationthe reaction mixture was concentrated in vacuo
3. dissolutiondissolved in DCM
4. washwas washed with DCM, MeOH
5. additionThe product containing fractions
6. concentrationconcentrated in vacuo
7. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)