1,2-Dichloroethane → N1-(3-Fluoro-4-(2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-(2-methoxyphenyl)malonamide

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Reaction Steps

A solution of 3-fluoro-4-(2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)thieno[3,2-b]pyridin-7-yloxy)aniline (230) (50 mg, 0.110 mmol), 3-(2-methoxyphenylamino)-3-oxopropanoic acid 27 (34 mg, 0.165 mmol) (scheme 8), EDC (25 mg, 0.165 mmol) and HOBt (22 mg, 0.165 mmol) in DMF (1.1 mL) was stirred overnight at room temperature. More 27 (34 mg, 0.165 mmol) and EDC (25 mg, 0.165 mmol) were added and the mixture stirred for a further 6 h. The mixture was diluted with EtOAc, extracted with water, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was re-dissolved in MeOH and purified by preparative HPLC (gradient 40% to 95% MeOH in water, 45 min) followed by flash chromatography (MeOH/CHCl3/NH4Cl 1:9:0.1) giving title compound 224 (19 mg, 0,056 mmol, 51% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 10.61 (s, 1H), 9.64 (s, 1H), 8.45 (d, J=5.5 Hz, 1H), 8.07 (dd, J=8.8 Hz, J=1.4 Hz, 1H), 7.86 (dd, J=2.3 Hz, J=13.1 Hz, 1H), 7.49-7.41 (m, 3H), 7.11-7.05 (m, 2H), 6.92 (m, 1H), 6.61 (dd, J=0.8 Hz, J=5.5 Hz, 1H), 6.43 (m, 1H), 3.86 (s, 3H), 3.64 (s, 2H), 3.33 (m, 2H), 2.52-2.50 (m, 2H), 2.49 (m, 2H), 2.36-2.33 (m, 5H). MS (m/z): 547.42 (100% yield).

Provenance & Evidence