Hydrochloric Acid → HCID 178482118, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[methyl(phenyl)amino]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Example 3.174 step 2, 160 mg, 0.339 mmol) in methanol (2 mL) in a sealable tube was added 30% sodium hydroxide solution (4 mL). The tube was sealed and heated to 80° C. for 14 hours. The reaction mixture was cooled to room temperature and neutralized with the addition of 1.5 M HCl solution. The solution was extracted with ethyl acetate (4×25 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by preparative HPLC (Kromasil C18, water/acetonitrile+0.1% TFA modifier) to afford 4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[methyl(phenyl)amino]-3H-imidazo[4,5-c]pyridine-6-carboxylic acid (TFA salt). MS ES/APCl calc'd. for C27H28ClN6O2 [M+H]+ 490. found 490. 1H NMR (400 MHz, DMSO-d6): δ 12.79 (bs, 1H), 8.78 (d, J=12.8 Hz, 2H), 8.30 (s, 1H), 7.82 (s, 1H), 7.26 (t, J=7.6 Hz, 2H), 6.96-6.87 (m, 3H), 3.40-3.30 (m, 2H), 3.21 (s, 3H), 1.46-1.42 (m, 2H), 1.26-1.01 (m, 4H), 0.86-0.84 (m, 3H), 0.73-0.71 (m, 4H). The compounds in Table 3 were prepared as described above or using procedures which were analogous to those described above. In some cases, enantiomers or diastereomers were separated by chromatography on chiral columns using standard techniques. Amines used to displace the bromide of Preparative Example 3.1 are described above, commercially available, known in the literature, or can be prepared using methods readily available in the literature.

Provenance & Evidence