56622-54-9

3-Aminomethyl-6-methylpyridine is used in the synthesis of non-nucleoside phthalimide derivatives as HIV-1 reverse transcriptase inhibitors. Also used in in the discovery of potent nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with cytocrhome P450 CYP2C9 inhibitory activity.

Example 4: 106 Synthesis of Step 1: Under argon protection, 3.00 g (22.0 mmol) of 6-methylnicotinamide was dissolved in 10 ml of tetrahydrofuran (THF), followed by the slow addition of 34 ml (34 mmol; 1.5 eq.) of 1 M lithium aluminium hydride in THF solution. After 45 min of reaction, 1.22 g (1.5 eq.) of lithium aluminum hydride dissolved in 40 ml of THF was added to the system. The reaction mixture was heated to 60°C under stirring and maintained at this temperature for 24 hours. Upon completion of the reaction, the reaction was carefully quenched sequentially with isopropanol, methanol and water at 0°C under stirring. Subsequently, the solvent was evaporated under reduced pressure. To the residue, 100 ml of 2N NaOH solution and 100 ml of dichloromethane (DCM) were added and centrifuged to separate the resulting white precipitate. The aqueous layer was extracted four times with 60 ml of DCM. All organic layers were combined, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to remove the solvent to afford 1.57 g (12.9 mmol; 58% yield) of the target product, 3-aminomethyl-6-methylpyridine (amine 2), which was used directly in the subsequent reaction without further purification.

[1] Patent: WO2006/128670, 2006, A1. Location in patent: Page/Page column 113