反应详情

The solution of 2-chloro-6-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl]-5-phenylnicotinonitrile (1-6; 0.040 g, 0.077 mmol) and hydrazine (0.2 mL) in EtOH (2 mL) was heated to 130° C. in microwave for 10 min. The mixture was concentrated, treated with aqueous Na2CO3 solution (5 mL, 2 M) and extracted with CH2Cl2 (3×10 mL). The combined organic layer was dried, filtered and concentrated. The residue was purified by silica gel chromatography (3-5% MeOH in CH2Cl2) to give 1-{1-[4-(3-amino-5-phenyl-1H-pyrazolo[3,4-b]pyridin-6-yl)benzyl]piperidin-4-yl}-1,3-dihydro-2H-benzimidazol-2-one (1-7). 1H-NMR (500 MHz, CDCl3) δ 9.89 (s, 1H), 8.71 (s, 1H), 7.95 (s, 1H), 7.35 (d, J=8.1, 2H), 7.18-7.27 (m, 8H), 6.98-7.05 (m, 2H), 6.85 (d, J=7.5, 1H), 4.33-4.36 (m, 1H), 4.21 (s, 2H), 3.55 (s, 2H), 3.00-3.02 (m, 2H), 2.41-2.47 (m, 2H), 2.13-2.17 (m, 2H), 1.77-1.79 (m, 2H). LRMS m/z (M+H) Calcd: 516.5, found: 516.2.

1. concentrationThe mixture was concentrated
2. additiontreated with aqueous Na2CO3 solution (5 mL, 2 M)
3. extractionextracted with CH2Cl2 (3×10 mL)
4. customThe combined organic layer was dried
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by silica gel chromatography (3-5% MeOH in CH2Cl2)