反应详情

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (78 mg, 0 2 mmol), (azetidin-3-ylmethyl)methyloxetan-3-yl-amine (47 mg, 0 3 mmol), and 4 Å molecular sieves (250 mg) in 1,2-dichloroethane (2 mL) was stirred at RT for 6 h. Sodium triacetoxyborohydride (85 mg, 0.4 mmol) was added and the resulting reaction mixture was stirred at RT under nitrogen atmosphere for 16 h. The suspension was filtered through Celite and the filtrate was concentrated in vacuo. The crude residue was loaded on an Isolute® SCX-2 cartridge (5 g). The cartridge was washed with DCM/MeOH and the desired product was subsequently eluted using a mixture of 2M NH3 in MeOH and DCM. The residue was purified by column chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 8:92) to afford 421 as an off-white foam (63 mg, 59%). LCMS (Method I): RT 2.11 min, [M+H]+ 532. 1H NMR (400 MHz, CDCl3): δ 7.97-7.96 (1 H, m), 7.72-7.71 (1 H, m), 7.23 (2 H, t, J=3.78 Hz), 4.61 (2 H, t, J=6.53 Hz), 4.53 (2 H, t, J=6.23 Hz), 4.32 (4 H, s), 3.82-3.81 (9 H, m), 3.51-3.50 (3 H, m), 3.32 (2 H, q, J=7.48 Hz), 3.03-2.89 (2 H, m), 2.68-2.57 (1 H, m), 2.40 (2 H, d, J=7.26 Hz), 2.04 (3 H, s), 1.41 (3 H, t, J=7.47 Hz)

1. customthe resulting reaction mixture
2. stirringwas stirred at RT under nitrogen atmosphere for 16 h
3. filtrationThe suspension was filtered through Celite
4. concentrationthe filtrate was concentrated in vacuo
5. washThe cartridge was washed with DCM/MeOH
6. washthe desired product was subsequently eluted
7. additiona mixture of 2M NH3 in MeOH and DCM
8. customThe residue was purified by column chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 8:92)