2-BroMo-5-trifluoroMethyl-pyrazine

To a suspension of Example 3B (0.08 g, 0.249 mmol) in N, N-dimethylformamide (0.5 mL, 6.46 mmol) were added N, N-diisopropylethylamine (0.174 mL, 0.996 mmol) and 2-bromo- 5-(trifluoromethyl)-pyrazine (0.068 g, 0.299 mmol). The reaction mixture was stirred overnight at 90 C, and then it was concentrate under reduced pressure at 50 C. The residue was purified by flash column chromatography on silica gel (12 g) eluted with heptane and ethyl acetate (0 to 100%) to give 40 mg of the title compound (37.3% yield) as a white solid. JH NMR (400 MHz, DMSO- ) delta ppm 8.78 (s, 1H), 8.59 (s, 1H), 8.44 (s, 1H), 7.99 (s, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.27 (d, J = 2.8 Hz, 1H), 6.99 (dd, J = 9.0, 2.9 Hz, 1H), 4.51 (s, 2H), 2.37 (s, 6H); 19F NMR (376 MHz, DMSO- ) delta ppm -64.83, -114.06; MS (ESI+) m/z 447 (M+H)+.To a suspension of N-(3-aminobicyclo[l . l . l]pentan-l-yl)-2-(3, 4- dichlorophenoxy)acetamide hydrochloride (0.08 g, 0.237 mmol, Example 2B) in N, N- dimethylformamide (0.5 mL, 6.46 mmol) was added N, N-diisopropylethylamine (0.166 mL, 0.948 mmol) followed by A 4 mL vial, equipped with a magnetic stir bar, was charged with N-(4- aminobicyclo[2.2.2]octan- 1 -yl)-2-(4-chloro-3-fluorophenoxy)acetamide hydrochloride (Example 1C, 28.2 mg, 0.078 mmol), To a suspension of N-(3-aminobicyclo[1.1.1]pentan-1-yl)-2-(3, 4- dichlorophenoxy)acetamide hydrochloride (0.08 g, 0.237 mmol, Example 2B) in N, N- dimethylformamide (0.5 mL, 6.46 mmol) was added N, N-diisopropylethylamine (0.166 mL, 0.948 mmol) followed by A 4 mL vial, equipped with a magnetic stir bar, was charged with N-(4- aminobicyclo[2.2.2]octan-1-yl)-2-(4-chloro-3-fluorophenoxy)acetamide hydrochloride (Example 1C, 28.2 mg, 0.078 mmol), To a suspension of Example 3B (0.08 g, 0.249 mmol) in N, N-dimethylformamide (0.5 mL, 6.46 mmol) were added N, N-diisopropylethylamine (0.174 mL, 0.996 mmol) and 2- bromo-5-(trifluoromethyl)-pyrazine (0.068 g, 0.299 mmol). The reaction mixture was stirred overnight at 90 C, and then it was concentrate under reduced pressure at 50 C. The residue was purified by flash column chromatography on silica gel (12 g) eluted with heptane and ethyl acetate (0 to 100%) to give 40 mg of the title compound (37.3% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) delta ppm 8.78 (s, 1H), 8.59 (s, 1H), 8.44 (s, 1H), 7.99 (s, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.27 (d, J = 2.8 Hz, 1H), 6.99 (dd, J = 9.0, 2.9 Hz, 1H), 4.51 (s, 2H), 2.37 (s, 6H); 19F NMR (376 MHz, DMSO-d6) delta ppm -64.83, -114.06; MS (ESI+) m/z 447 (M+H)+.

Molecular Weight:226.98
XLogP3:1.7
Hydrogen Bond Acceptor Count:5
Exact Mass:225.93535
Monoisotopic Mass:225.93535
Topological Polar Surface Area:25.8
Heavy Atom Count:11
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes