3-chloro-4-fluoro-N,N-dimethylbenzamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 18) (206 mg, 0.6 mmol), 3-chloro-4-fluoro-N,N-dimethyl-benzamide (CAS no. 871657-07-7) (192 mg, 0.9 mmol) and potassium carbonate (166 mg, 1.2 mmol) in N,N-dimethylacetamide (5 mL) was stirred at 160° C. for 6 hours. The solution was evaporated under reduced pressure, the residue dissolved in ethyl acetate (40 mL), washed with water (2×20 mL) and brine (10 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by flash chromatography on silica eluting with 0-4% methanol in DCM to afford the product (98 mg, 31%). 1H NMR δ (300 MHz, CDCl3) 2.10-2.27 (m, 1H), 2.54-2.67 (m, 1H), 2.55 (s, 3H), 2.93 (s, 3H), 2.98-3.19 (m, 6H), 3.34-3.57 (m, 2H), 4.92 (t, 1H), 6.86 (s, 1H), 7.06 (d, 1H), 7.16 (s, 1H), 7.33 (d, 1H), 7.40 (s, 1H), 7.57 (s, 1H), 8.13 (s, 1H), 8.53 (s, 1H), 9.51 (s, 1H); m/z 524 (M+H+). The solution was evaporated under reduced pressure the residue dissolved in ethyl acetate (40 mL) washed with water (2×20 mL) and brine (10 mL) dried (MgSO4) filtered the solvent removed under reduced pressure The residue was purified by flash chromatography on silica eluting with 0-4% methanol in DCM

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-hydroxy-5-[(3S)-1-methyl-2-oxo-pyrrolidin-3-yl]oxy-N-(5-methylpyrazin-2-yl)benzamide (Intermediate 18) (206 mg, 0.6 mmol), 3-chloro-4-fluoro-N,N-dimethyl-benzamide (CAS no. 871657-07-7) (192 mg, 0.9 mmol) and potassium carbonate (166 mg, 1.2 mmol) in N,N-dimethylacetamide (5 mL) was stirred at 160° C. for 6 hours. The solution was evaporated under reduced pressure, the residue dissolved in ethyl acetate (40 mL), washed with water (2×20 mL) and brine (10 mL), dried (MgSO4), filtered and the solvent removed under reduced pressure. The residue was purified by flash chromatography on silica eluting with 0-4% methanol in DCM to afford the product (98 mg, 31%). 1H NMR δ (300 MHz, CDCl3) 2.10-2.27 (m, 1H), 2.54-2.67 (m, 1H), 2.55 (s, 3H), 2.93 (s, 3H), 2.98-3.19 (m, 6H), 3.34-3.57 (m, 2H), 4.92 (t, 1H), 6.86 (s, 1H), 7.06 (d, 1H), 7.16 (s, 1H), 7.33 (d, 1H), 7.40 (s, 1H), 7.57 (s, 1H), 8.13 (s, 1H), 8.53 (s, 1H), 9.51 (s, 1H); m/z 524 (M+H+). The solution was evaporated under reduced pressure the residue dissolved in ethyl acetate (40 mL) washed with water (2×20 mL) and brine (10 mL) dried (MgSO4) filtered the solvent removed under reduced pressure The residue was purified by flash chromatography on silica eluting with 0-4% methanol in DCM