Dimethylformamide → HCID 59411413, compound

Participants

Reaction Conditions

Reaction Steps

Methyl 5-(3-(tert-butoxycarbonyl)methyl)carbamoyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-2-methoxy-6-methylnicotinate. To a degassed solution containing palladium (II) acetate (0.014 g, 0.063 mmol) and DMF (0.70 mL) was added 1,1′-Bis(diphenylphosphino)ferrocene. The solution was heated to 50° C. and maintained for 15 minutes. The solution was cooled to room temperature and 3-(tert-butoxycarbonyl(methyl)carbamoyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-ylboronic acid (0.10 g, 0.21 mmol) and methyl 5-bromo-2-methoxy-6-methylnicotinate (0.054 g, 0.21 mmol) were added. Triethylamine was then added and the solution was heated at 90° C. for 3 h. The mixture was cooled to room temperature, filtered to remove solids and concentrated. Purification on silica gel (0-75% ethyl acetate/hexanes, 60 min gradient, 25 g column) afforded methyl 5-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-2-methoxy-6-methylnicotinate as a white residue. 1H NMR (400 MHz, MeOD) δ ppm 8.60 (1H, d, J=7.03 Hz), 8.13 (1H, s), 7.77 (2H, d, J=3.26 Hz), 7.75 (1H, s), 7.24 (2H, s), 6.99 (1H, s), 4.07 (3H, s), 3.89 (3H, s), 3.29 (3H, s), 2.45 (3H, s), 1.01-1.13 (9H, m). LCMS retention time: 3.803 mM. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 3 micron, C18, 2.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 10% CH3CN/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3CN/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 567 (MH+).

Provenance & Evidence