Glycolic Acid → HCID 57542359, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of (R)-tert-butyl 2-((5-fluoro-2-(3-fluorophenethylamino)-6-(1-methyl-1H-pyrazol-4-yl)nicotinamido)methyl)azetidine-1-carboxylate (16.5 g, 31.4 mmol) in 100 mL DCM at 0° C. was added trifluoroacetic acid (24 mL, 314 mmol) slowly. The mixture was stirred at r.t for 2 hours until the Boc protection group was completely removed. The mixture was then concentrated. The residue was dissolved in 100 mL DMF and cooled down to 0° C. To the mixture was added a mixture of glycolic acid (2.86 g, 38 mmol), HBTU (14.3 g, 38 mmol), HOBT (5.1 g, 38 mmol) and DIEA (16.4 ml, 94 mmol). The mixture was warmed up to r.t and stirred at r.t. for 2 hours. The mixture was extracted with EtOAc. The organic layer was further washed with 1N NaOH (300 ml) and brine, dried and concentrated. The residue was subjected to a Biotage silica gel chromatography using gradient 0-40% B as eluant (A=dichloromethane, B=10% MeOH in dichloromethane) to give the crude product. The yellow solid was further tritirated with 100 mL EtOAc. (R)-5-fluoro-2-(3-fluorophenethylamino)-N-((1-(2-hydroxyacetyl)azetidin-2-yl)methyl)-6-(1-methyl-1H-pyrazol-4-yl)nicotinamide was obtained as a pale yellow solid (12.7 g, 83% yield). LRMS (M+H+) m/z 485.1.

Provenance & Evidence