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

Participants

Reaction Conditions

Reaction Steps

To a solution of N-[(3-bromo-4-fluorophenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-1,3-benzenedicarboxamide (0.166 g, 0.26 mmol) in 1,4-dioxane (3 mL) and H2O (1 mL) was added 1,1-dimethylethyl 4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperidinecarboxylate (0.157 g, 0.390 mmol), Pd(Ph3P)4 (0.015 g, 0.013 mmol), and K2CO3 (0.144 g, 1.040 mmol). This mixture was heated in a microwave at 130° C. for 15 min. The organic layer was separated, filtered, concentrated, and purified with a Gilson HPLC (with 0.1% TFA). Before the sample was concentrated with GeneVav EZ-2, TFA (5 drops) was added to each tube (12 mL). The resultant mixture was concentrated, purified with a Gilson HPLC (with 0.1% TFA), concentrated, and basified with an amino cartridge to afford 0.0738 g (39%) of the title compound. LC-MS m/z 732 (M+H)+; 1H NMR (400 MHz, CD3OD) δ ppm 1.36-1.52 (m, 8 H) 1.81-1.93 (m, 4 H) 2.09 (d, J=11.54 Hz, 2 H) 2.62-2.70 (m, 2 H) 2.87-2.98 (m, 2 H) 3.16 (q, 2 H) 3.19-3.30 (m, 1 H) 3.32-3.39 (m, J=12.55 Hz, 2 H) 3.62-3.71 (m, 2 H) 3.99-4.07 (m, 2 H) 4.29-4.40 (m, J=4.27, 4.27 Hz, 1 H) 4.48 (q, J=7.11 Hz, 2 H) 4.60 (s, 2 H) 4.68-4.75 (m, 2 H) 7.14 (dd, J=10.54, 8.53 Hz, 1 H) 7.18-7.26 (m, 1 H) 7.33-7.44 (m, 4 H) 7.44-7.50 (m, J=7.53, 2.26 Hz, 1 H) 7.59 (t, J=7.78 Hz, 1 H) 8.01-8.08 (m, 2 H) 8.28 (s, 1 H) 8.39 (s, 1 H).

Provenance & Evidence