4-(5-chloropyridin-3-yl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile (product of Step 2, Preparative Example 3.1) (500 mg, 1.367 mmol) was dissolved in THF (13.7 mL) and cooled to −78° C. in a flask under nitrogen before adding lithium magnesium 2,2,6,6-tetramethylpiperidin-1-ide dichloride, 1.0 M in THF (3.01 mL, 3.01 mmol). After stirring at −78° C. for 45 minutes, cyclopentanecarbaldehyde (321 μL, 3.01 mmol) was added, and the reaction was allowed to stir at −78° C. for 30 minutes before removing the cooling bath. After warming to room temperature over 1 hr, the reaction mixture was quenched with sat. aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography (hexanes/0-65% EtOAc) to afford 4-(5-chloropyridin-3-yl)-2-(cyclopentyl(hydroxy)methyl)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C26H30ClN5O [M+H]+ 464. found 464. 1H NMR (600 MHz, CD3OD) δ 8.78 (d, J=2.1, 1H), 8.74 (d, J=1.3, 1H), 8.27-8.24 (m, 1H), 8.23 (s, 1H), 4.68 (d, J=9.1, 1H), 4.15-3.88 (m, 2H), 2.73 (dd, J=8.0, 16.0, 1H), 1.99-1.91 (m, 1H), 1.76-1.54 (m, 6H), 1.50 (d, J=13.3, 2H), 1.31-1.22 (m, 1H), 1.19-1.09 (m, 1H), 1.02-0.96 (m, 1H), 0.92-0.77 (m, 4H), 0.75 (d, J=6.5, 3H), 0.60-0.47 (m, 2H).
