反应详情

A mixture of 9-methyl-2-(2-methylbenzoimidazol-1-yl)-6-morpholin-4-yl-9H-purine-8-carbaldehyde (72 mg, 0.19 mmol), methylpiperidin-4-yl(tetrahydrofuran-3-yl)amine (42 mg, 0.23 mmol) and 4 Å powdered molecular sieves (200 mg) in DCE (5 mL) was stirred at room temperature for 4 h before the addition of sodium triacetoxyborohydride (81 mg, 0.38 mmol). The reaction mixture was stirred for 16 h then filtered through celite, washing with DCM. The organic phase was washed with brine (×1) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%). The resulting oil was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH affording 389 as a white solid (55 mg, 53%). LCMS (Method G): RT 4.96 min [M+H]+ 546.3. 1H NMR (CDCl3, 400 MHz): δ 8.11-8.07 (m, 1 H); 7.73-7.69 (m, 1 H); 7.29-7.24 (m, 2 H); 4.35 (m, 4 H); 3.96 (m, 1 H); 3.92-3.80 (m, 8 H); 3.83-3.71 (m, 4 H); 3.43 (m, 1 H); 3.02-2.90 (m, 4 H); 2.52 (m, 1 H); 2.26 (s, 3 H); 2.16 (m, 2 H); 2.03 (m, 1 H); 1.90 (m, 1 H); 1.77 (s, 3 H) and 1.59 (m, 2 H)

1. filtrationthen filtered through celite
2. washwashing with DCM
3. washThe organic phase was washed with brine (×1)
4. concentrationconcentrated in vacuo
5. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%)
6. washwas washed with MeOH/DCM
7. washthe product eluted with 2M NH3/MeOH affording 389 as a white solid (55 mg, 53%)
8. customRT 4.96 min [M+H]+ 546.3