N′-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)-2-(5-oxo-1,6-naphthyridin-6(5H)-yl)propanehydrazide (400 mg, 982 μmol) and triphenylphosphine (386 mg, 1.4 mmol) were taken up in THF (9.8 mL). TMS-azide (195 μl, 1.4 mmol) was added, followed by slow addition of DEAD (233 μl, 1.4 mmol) and the reaction was stirred at room temperature for 1 hr until complete. The reaction was concentrated and purified via MPLC with a gradient 100% DCM to 90% DCM/10% MeOH/1% NH4OH to yield racemic 6-(1-(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)-1,6-naphthyridin-5(6H)-one (220 mg, 57% yield) as a tan solid. Separated by preperative SFC (ChiralPak® OJ-H, (20×150 mm, 5 □m), 20% MeOH, 80% CO2, 0.2% DEA; 100 bar system pressure; 70 mL/min; tr: 3.5 min) to yield (R)-6-(1-(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)-1,6-naphthyridin-5(6H)-one (60 mg, 15% yield). On the basis of previous crystallographic data and potency recorded for related compound in the same program, the absolute stereochemistry has been assigned to be the R enantiomer. MS m/z=390.2 [M+H], calc 389.14 for C20H16FN7O. 1H NMR (400 MHz, CHLOROFORM-d) □ ppm 2.16 (d, J=5.18 Hz, 3 H) 3.97 (s, 3 H) 6.82 (d, J=6.55 Hz, 1 H) 7.01-7.13 (m, 2 H) 7.41-7.49 (m, 1 H) 7.54 (d, J=6.26 Hz, 1 H) 7.61 (s, 1 H) 7.71 (s, 1 H) 8.33 (s, 1 H) 8.78 (d, J=7.73 Hz, 1 H) 8.93 (s, 1 H).
