tert-butyl (2R)-2-(aminomethyl)azetidine-1-carboxylate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 5-fluoro-2-(3-fluorophenethylamino)-6-(1-methyl-1H-pyrazol-4-yl)nicotinic acid (14.3 g, 40 mmol) and DMF (300 mL) was added of HBTU (18.2 g, 48 mmol) and HOBT (6.49 g, 48 mmol). The mixture was cooled down to 0° C., 8.93 g (48 mmol) of (R)-tert-butyl 2-(aminomethyl)azetidine-1-carboxylate was added, followed by 13.9 ml of DIEA (80 mmol). The mixture was stirred at r.t for 1 hour and extracted with 300 mL EtOAc. The organic layer was washed with 500 mL brine, dried over MgSO4 and then concentrated. The residue was purified by Biotage silica gel chromatography using EtOAc:Hex (1:1) as eluant. (R)-tert-butyl 2-((5-fluoro-2-(3-fluorophenethylamino)-6-(1-methyl-1H-pyrazol-4-yl)nicotinamido)methyl)azetidine-1-carboxylate was obtained as a yellow solid (16.5 g, yield 80%). LRMS (M+H+) m/z 527.1. extracted with 300 mL EtOAc The organic layer was washed with 500 mL brine dried over MgSO4 concentrated The residue was purified by Biotage silica gel chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of (R)-tert-butyl 2-(azidomethyl)azetidine-1-carboxylate (17 g, 80 mmol), 10% Pd/C (2 g) and MeOH (150 mL) was stirred under 45 psi hydrogen for 1 hour. The catalyst was filtered off and the filtrate was concentrated to give (R)-tert-butyl 2-(aminomethyl)azetidine-1-carboxylate (14.9 g, yield 100%). LRMS (M+H+) m/z 187.3. The catalyst was filtered off the filtrate was concentrated