Trifluoroacetic acid → n-{[1,6-Diethyl-4-(tetrahydro-2h-pyran-4-ylamino)-1h-pyrazolo[3,4-b]pyridin-5-yl]methyl}-n'-{[3'-(4-piperidinylmethyl)-3-biphenylyl]methyl}-1,3-benzenedicarboxamide

Participants

Reaction Steps

To a solution of 3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]benzoic acid (0.03 g, 0.066 mmol) in DCM (0.66 mL) was added 1,1-dimethylethyl 4-{[3′-(aminomethyl)-3-biphenylyl]methyl}-1-piperidinecarboxylate (0.025 g, 0.066 mmol), HBTU (0.028 g, 0.073 mmol), and TEA (0.014 mL, 0.100 mmol). This mixture was stirred at room temperature for 18 h. The reaction mixture was concentrated (Glas-Col), purified using a Gilson HPLC (with 0.1% TFA) and concentrated with GeneVav EZ-2 evaporator. To the resultant mixture was added DCM (0.1 mL) and TFA (0.033 mL, 0.428 mmol). The resultant mixture was left at room temperature for 30 min before being concentrated on Glas-Col evaporator, purified using a Gilson HPLC (with 0.1% TFA), concentrated with GeneVav EZ-2 and basified with an amine cartridge to afford 0.0245 g (51.7%) of the title compound. LC-MS m/z 714 (M+H)+; 1H NMR (400 MHz, CD3OD) δ ppm 1.35-1.45 (m, J=7.40, 7.40 Hz, 4 H) 1.44-1.53 (m, J=7.15, 7.15 Hz, 4 H) 1.80-1.96 (m, J=13.80 Hz, 5 H) 2.08 (d, J=12.30 Hz, 2 H) 2.66 (d, J=6.53 Hz, 2 H) 2.92 (t, J=12.55 Hz, 2 H) 3.15 (q, J=7.45 Hz, 2 H) 3.35 (d, J=14.31 Hz, 2 H) 3.65 (t, J=11.29 Hz, 2 H) 4.02 (d, J=11.04 Hz, 2 H) 4.27-4.39 (m, 1 H) 4.47 (q, J=7.19 Hz, 2 H) 4.64 (s, 2 H) 4.70 (s, 2 H) 7.16 (d, J=7.28 Hz, 1 H) 7.30-7.54 (m, 6 H) 7.55-7.65 (m, 2 H) 8.05 (d, J=7.78 Hz, 2 H) 8.27 (s, 1 H) 8.40 (s, 1 H).

Provenance & Evidence