Diisopropylethylamine → N-[((1S,4S,6S)-3-{[6-Methyl-3-(2-pyrimidinyl)-2-pyridinyl]carbonyl}-3-azabicyclo[4.1.0]hept-4-yl)methyl]-5-(trifluoromethyl)-2-pyridinamine

Participants

Reaction Steps

To a solution of 6-methyl-3-(2-pyrimidinyl)-2-pyridinecarboxylic acid D19 (99 mg), DIPEA (0.066 ml, 0.376 mmol) and N-[(1S,4S,6S)-3-azabicyclo[4.1.0]hept-4-ylmethyl]-5-(trifluoromethyl)-2-pyridinamine D12 (34 mg) in DCM (3 ml), stirred under nitrogen at room temperature was added TBTU (60.4 mg, 0.188 mmol) in one charge. The reaction mixture was stirred at room temperature for 5 hours. NaHCO3 aqueous saturated solution was added and the aqueous extracted with DCM, the phases were separated on a hydrophobic frit and the combined organic solvent was removed to give the crude product which was purified by flash chromatography (silica —NH 11 g column, gradient elution from Cy to Cy/EtOAc 2:8 in 30 minutes, flow rate 30 mls/minute). The product so obtained was purified a second time by flash chromatography (silica —NH 11 g column gradient elution from Cy to Cy/EtOAc 1:1 in 20 minutes, flow rate 30 mls/minute) to afford the title compound E3 (21 mg). UPLC (Acid GEN_QC): rt1=0.68 minutes, peak observed: 469 (M+1). C24H23F3N6O requires 460. 1H NMR (500 MHz, CDCl3) δ ppm 0.08-0.16 (m, 1 H), 0.73-0.81 (m, 1 H), 0.82-1.32 (m, 3H), 2.46-2.58 (m, 2 H), 2.66 (s, 3 H), 3.52-3.69 (m, 2 H), 3.70-3.80 (m, 1 H), 4.47-4.66 (m, 1 H), 6.38-6.50 (m, 1 H), 6.74-7.01 (m, 1 H), 7.08 (t, 1 H), 7.35 (d, 1 H), 7.47 (d, 1 H), 8.33 (s, 1 H), 8.54-8.64 (m, 3 H).

Provenance & Evidence