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

Participants

Reaction Steps

3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(3,3,3-trifluoropropyl)furo[2,3-b]pyridin-5-yl)benzoic acid (30 mg, 0.062 mmol) was taken up in DMF (1 ml) and treated with N-ethyl-N-isopropylpropan-2-amine (32 μl, 0.19 mmol), 2-(3-methyl-1,2,4-oxadiazol-5-yl)propan-2-amine hydrochloride (13 mg, 0.074 mmol) followed by 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (35 mg, 0.093 mmol). The reaction was allowed to stir for 1 h. The crude material was purified via preparative LC/MS with the following conditions: Column:Waters XBridge C18, 19×200 mm, 5-μm particles; Guard Column:Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: water with 20-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 20-mM ammonium acetate; Gradient: 40-80% B over 20 minutes, then a 5-minute hold at100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The yield of the product was 18.1 mg, and its estimated purity by LCMS analysis was 98%. Two analytical LC/MS injections were used to determine the final purity. Injection 1 conditions: Column:Waters BEH C18, 2.0×50 mm, 1.7-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 40° C.; Gradient: 0.5 min hold at 0% B, 0-100% B over 4 minutes, then a 0.5-minute hold at 100% B; Flow: 1 mL/min. retention time: 3.02 min; M+H: 610. Injection 2 conditions: Column:Waters BEH C18, 2.0×50 mm, 1.7-μm particles; Mobile Phase A: 5:95 methanol:water with 10 mM ammonium acetate; MobilePhase B: 95:5 methanol:water with 10 mM ammonium acetate; Temperature: 40° C.; Gradient: 0.5 min hold at 0% B, 0-100% B over 4 minutes, then a 0.5-minute hold at 100% B; Flow: 0.5 mL/min. retention time: 4.06 min; M+H: 610. Proton NMR was acquired in deuterated DMSO. 1H NMR (500 MHz, DMSO-d6) δ 9.03 (s, 1H), 8.56-8.46 (m, 1H), 8.09-7.99 (m, 2H), 7.98-7.86 (m, 3H), 7.68-7.58 (m, 2H), 7.41 (t, J=8.7 Hz, 2H), 3.04-2.95 (m, 2H), 2.84-2.69 (m, 5H), 1.70 (s, 6H).

Provenance & Evidence