Cesium carbonate → 3-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)-5-(6-methylsulfonylpyridin-3-yl)oxy-benzamide

Participants

Reaction Steps

A mixture 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 18) (305 mg, 0.6 mmol), 5-bromo-2-methylsulfonyl-pyridine (CAS no. 98626-95-0) (142 mg, 0.6 mmol), cesium carbonate (390 mg, 1.2 mmol) and tris(triphenylphosphine)copper bromide (CAS no. 15709-74-7) (112 mg, 0.12 mmol) in N,N-dimethylacetamide (5 mL) was stirred in the microwave at 160° C. for 6 hours. N,N-Dimethylacetamide was removed by evaporation under reduced pressure. The residue was partitioned between ethyl acetate (30 mL) and water (50 mL). The organic phase was separated and the aqueous layer was acidified with hydrochloric acid (1N, 5 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography on silica eluting with 0-5% methanol in DCM to afford the product (120 mg, 40%). 1H NMR δ (300 MHz, CDCl3) 2.14-2.32 (m, 1H), 2.52-2.69 (m, 1H), 2.55 (s, 3H), 2.94 (s, 3H), 3.23 (s, 3H), 3.35-3.59 (m, 2H), 4.96 (t, 1H), 7.05 (s, 1H), 7.27 (s, 1H), 7.48 (d, 1H), 7.54 (s, 1H), 8.07 (d, 1H), 8.14 (s, 1H), 8.49 (s, 1H), 8.55 (s, 1H), 9.51 (s, 1H); m/z 498 (M+H+).

Provenance & Evidence