Methanesulfonamide → HCID 66657392, compound

Participants

Reaction Steps

A mixture of the chloride from preparation 261 (50 mg, 0.1 mmol), N-ethyldiisopropylamine (0.05 mL, 0.3 mmol), N-ethylmethylamine (0.026 mL, 0.3 mmol) and cesium fluoride (15 mg, 0.1 mmol) in 1-methyl-2-pyrrolidinone (1 mL) was heated in a Reactivial® at 110° C. for 90 minutes. The cooled reaction mixture was purified directly using a Phenomenex Luna C18 column reverse phase column and acetonitrile:95% water/5% methanol/0.1% trifluoroacetic acid (5:95 to 95:5) as elution gradient. The product was dissolved in dichloromethane and the solution washed with sodium bicarbonate solution, dried over magnesium sulphate and evaporated under reduced pressure to provide the title compound, 24 mg. Alternatively, example 178 may be prepared by the method of examples 172-177. 4-Dimethylaminopyridine (22 mg, 0.20 mmol) was added to a solution of the acid from example 127 (70 mg, 0.15 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (38 mg, 0.20 mmol) and methanesulphonamide (19 mg, 0.20 mmol) in dichloromethane (2 ml) and the reaction stirred at room temperature for 18 hours. The mixture was diluted with dichloromethane (20 mls) and 1M citric acid solution (10 ml), then the phases separated. The organic phase was purified directly by column chromatography on silica gel (using a Parallel Flashmaster system) using an elution gradient of methanol:dichloromethane (0:100 to 2:98) to provide the title compound as a yellow solid. 1H NMR (DMSO-D6+1 drop TFAd, 400 MHz) δ: 1.19 (t, 3H), 2.49 (s, 3H), 3.20 (s, 3H), 3.41 (s, 3H), 3.66 (q, 2H), 4.06 (q, 2H), 4.14 (t, 2H), 5.03 (t, 2H), 7.20 (d, 1H), 8.12 (s, 1H), 8.27 (d, 1H). MS ES− m/z 529 [M-H]−

Provenance & Evidence