Piperidin-4-ol → N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-({6-fluoro-3'-[(4-hydroxy-1-piperidinyl)methyl]-3-biphenylyl}methyl)-1,3-benzenedicarboxamide

Participants

Reaction Steps

To a solution of N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(6-fluoro-3′-formyl-3-biphenylyl)methyl]-1,3-benzenedicarboxamide (0.133 g, 0.2 mmol) in DCM (3 mL) was added 4-piperidinol (0.021 g, 0.210 mmol), NaBH(OAc)3 (0.051 g, 0.240 mmol). This mixture was stirred at room temperature for 15 h at which time more 4-piperidinol (0.004 g, 0.04 mmol) was added and stirring continued for 2 h. Then more NaBH(OAc)3 (0.025 g, 0.1 mmol) was added and the mixture was stirred for an additional 2 h. The reaction mixture was filtered, concentrated, and purified using a Gilson HPLC (with 0.1% TFA). The fraction was concentrated and basified with an amine cartridge to afford 0.1067 g of the title compound. LC-MS m/z 748 (M+H)+; 1H NMR (400 MHz, CD3OD) δ ppm 1.40 (t, J=7.65 Hz, 3 H) 1.49 (t, J=7.15 Hz, 3 H) 1.62-1.83 (m, 1 H) 1.83-2.01 (m, 4 H) 2.05-2.27 (m, 3 H) 3.08 (t, J=12.05 Hz, 1 H) 3.16 (q, J=7.36 Hz, 2 H) 3.32-3.41 (m, 2 H) 3.53 (d, J=12.30 Hz, 1 H) 3.62-3.72 (m, 2 H) 3.76-4.10 (m, 3 H) 4.31-4.51 (m, 5 H) 4.61 (s, 2 H) 4.72 (s, 2 H) 7.18 (dd, J=10.67, 8.41 Hz, 1 H) 7.38-7.46 (m, 1 H) 7.50-7.63 (m, 4 H) 7.65-7.76 (m, 2 H) 8.01-8.09 (m, 2 H) 8.29 (s, 1 H) 8.40 (t, J=1.63 Hz, 1 H).

Provenance & Evidence