反应详情

A mixture of 9-methyl-2-(2-methylbenzoimidazol-1-yl)-6-morpholin-4-yl-9H-purine-8-carbaldehyde (78 mg, 0.2 mmol), (azetidin-3-ylmethyl)methyl(tetrahydrofuran-3-yl)amine (51 mg, 0.3 mmol) and 4 Å molecular sieves (250 mg) in 1,2-dichloroethane (2 mL) was stirred at RT under nitrogen atmosphere for 6 h. Sodium triacetoxyborohydride (85 mg, 0.4 mmol) was added and the resulting reaction mixture was stirred at RT for 36 h. The solvent was reduced in vacuo and the residue was loaded onto an Isolute® SCX-2 cartridge (5 g). The cartridge was washed with DCM/MeOH, the desired product was subsequently eluted using a mixture of 2M NH3 in MeOH and DCM. The residue was purified by column chromatography (Si—PCC, MeOH:DCM: gradient 0:100 to 10:90) to afford 419 as a white foam (80 mg, 73%). LCMS (Method I): RT 2.05 min, [M+H]+ 546. 1H NMR (400 MHz, CDCl3): δ 7.99-7.95 (1 H, m), 7.73-7.70 (1 H, m), 7.23 (2 H, m), 4.32 (4 H, s), 3.92 (1 H, m), 3.82-3.80 (7 H, m), 3.72 (1 H, q, J=8.06 Hz), 3.61 (1 H, m), 3.51 (2 H, t, J=7.19 Hz), 3.31 (2 H, q, J=7.48 Hz), 3.08 (1 H, m), 2.95 (2 H, t, J=6.81 Hz), 2.76-2.44 (2 H, m), 2.14 (3 H, s), 2.03-1.93 (1 H, m), 1.85-1.75 (1 H, m), 1.63 (4 H, br s), 1.41 (3 H, t, J=7.48 Hz)

1. customthe resulting reaction mixture
2. stirringwas stirred at RT for 36 h
3. washThe cartridge was washed with DCM/MeOH
4. washthe desired product was subsequently eluted
5. additiona mixture of 2M NH3 in MeOH and DCM
6. customThe residue was purified by column chromatography (Si—PCC, MeOH:DCM: gradient 0:100 to 10:90)