Diisopropylethylamine → 5-(3-((2-(1,2,4-oxadiazol-3-yl)propan-2-yl)carbamoyl)phenyl)-2-(4-fluorophenyl)-N-methyl-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridine-3-carboxamide

Participants

Reaction Steps

2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (117 mg, 0.308 mmol) was added to stirring solution of 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)benzoic acid (100 mg, 0.205 mmol), N-ethyl-N-isopropylpropan-2-amine (0.11 mL, 0.62 mmol) and 2-(1,2,4-oxadiazol-3-yl)propan-2-amine hydrochloride (50 mg, 0.31 mmol) in DMF (1 mL) at rt. The mixture was allowed to stir at rt for 1 h. The reaction mixture was then purified by preparative reverse phase HPLC on a C18 column using a suitably buffered H2O/CH3CN gradient, and concentrated to give the expected product 5-(3-((2-(1,2,4-oxadiazol-3-yl)propan-2-yl)carbamoyl)phenyl)-2-(4-fluorophenyl)-N-methyl-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridine-3-carboxamide (61 mg, 0.10 mmol, 49% yield)) consistent by LCMS and NMR. LC-MS retention time: 1.73 min; m/z (MH+): 597. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 3u C18 2.0×30 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 1 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode. 1H NMR (400 MHz, DMSO-d6) δ 9.43 (s, 1H), 8.70 (s, 1H), 8.40-8.32 (m, 1H), 8.01-7.94 (m, 2H), 7.93 (s, 1H), 7.90-7.85 (m, 1H), 7.69 (s, 1H), 7.64-7.57 (m, 2H), 7.38-7.31 (m, 2H), 6.63 (t, J=6.4 Hz, 1H), 4.26-4.12 (m, 2H), 2.80 (d, J=4.8 Hz, 3H), 1.70 (s, 6H).

Provenance & Evidence