反应详情

N2-{4-[4-amino-1-(4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-1-methyl-1H-2-indolecarboxamide (250 mg, 0.503 mmol), 2-methyl-1H-4-imidazolecarbaldehyde (83 mg, 0.755 mmol), sodium triacetoxyborohydride (159 mg, 0.755 mmol) and glacial acetic acid (30 mg, 0.554 mmol) were mixed in 1,2-dichloroethane (6 mL). The reaction mixture was stirred at room temperature overnight. Saturated sodium bicarbonate solution was added to adjust the pH to about 8. The layers were separated and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol/ammonium hydroxide (95:5:0.5 to 80:20:05) as mobile phase to give N2-[4-(4-amino-1-{1-[(2-methyl-1H-4-imidazolyl)methyl]-4-piperidyl}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-1-methyl-1H-2-indolecarboxamide (215 mg, 72%). 1H NMR (DMSO-d6) δ 1.91 (m, 2H), 2.23 (m, 7H), 3.00 (m, 2H), 3.41 (s, 2H), 3.96 (s, 3H), 4.04 (s, 3H), 4.78 (m, 1H), 6.72 (s, 1H), 7.15 (m, 1H), 7.32 (m, 4H), 7.78 (d, J=8.43 Hz, 1H), 7.70 (d, J=7.92 Hz, 1H), 8.11 (d, J=7.92 Hz, 1H), 8.24 (s, 1H), 9.44 (s, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, PH 4.5), 0.8 mL/min.): RT=2.00 min. MH+=591.3.

1. customThe layers were separated
2. extractionthe aqueous layer was extracted with dichloromethane
3. washThe combined organic layer was washed with brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. customevaporated
7. customThe residue was purified by flash column chromatography