Pyridine → N,N-dimethyl-5-[3-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-5-[(3-methyl-1,2,4-thiadiazol-5-yl)carbamoyl]phenoxy]pyrazine-2-carboxamide

Participants

Reaction Steps

1-Chloro-N,N,2-trimethyl-prop-1-en-1-amine (0.142 mL, 1.07 mmol) was added to a solution of 3-[5-(dimethylcarbamoyl)pyrazin-2-yl]oxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-benzoic acid (Intermediate 45) (358 mg, 0.9 mmol) in DCM (7 mL) and stirred at ambient temperature for 30 minutes. 3-Methyl-1,2,4-thiadiazol-5-amine (CAS no. 17467-35-5) (206 mg, 1.8 mmol) and pyridine (0.147 mL, 1.8 mmol) were added and the reaction stirred for 20 hours. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (15 mL) and DCM (15 mL), washed with water (10 mL) and filtered to give a solid which was washed with water and dried. The filtrate was washed with citric acid (1N, 10 mL), water (10 mL), saturated sodium bicarbonate solution (10 mL), brine (10 mL), dried (MgSO4) and evaporated. The residue was combined with the solid isolated from the filtration and purified by flash chromatography on silica eluting with a gradient of 0-3% methanol in DCM to afford the product (322 mg, 72%). 1H NMR δ (300 MHz, CDCl3) 1.93-2.06 (m, 1H), 2.45 (s, 3H), 2.55-2.66 (m, 1H), 2.80 (s, 3H), 3.03 (s, 6H), 3.19-3.53 (m, 2H), 5.14 (t, 1H), 7.30 (s, 1H), 7.63 (s, 1H), 7.72 (s, 1H), 8.43 (s, 1H), 8.58 (s, 1H), 11.9-12.8 (br s, 1H); m/z 498 (M+H+).

Provenance & Evidence