Reaction Steps
A mixture of 5-(4-chlorophenyl)-2,5-ethano-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3,4,5-tetrahydro-1H-2-benzoazepine (80 mg, 0.19 mmol) from Step B of Example 14, 2-bromo-5-methyl-1,3,4-thiadiazole (35 mg, 0.19 mmol) and potassium carbonate (81 mg, 0.58 mmol), in N,N-dimethylformamide (2 mL), was degassed with argon. Next, tetrakis(triphenylphosphine)palladium(0) (33 mg, 0.028 mmol) was added, the mixture was degassed again and heated to 100° C. After stirring for 17 h, the reaction mixture was cooled to ambient temperature, diluted with ethyl acetate (25 mL), washed with water (10 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC (90:9:1 methylene chloride/methanol/ammonium hydroxide). To the obtained material (6.3 mg, 0.016 mmol) in acetonitrile (1.5 mL) was added L-tartaric acid (2.5 mg, 0.016 mmol) in water (6 mL). The resultant solution was lyophilized to give 24544-chlorophenyl)-2,5-ethano-2,3,4,5-tetrahydro-1H-benzo[c]azepin-8-yl)-5-methyl-1,3,4-thiadiazole, L-tartrate salt (11 mg, 11%, AUC HPLC 98.7%) as a white solid: 1H NMR (CD3OD, 500 MHz) δ 7.90 (s, 1H), 7.64 (d, J=8.5 Hz, 1H), 7.47 (d, J=9.0 Hz, 2H), 7.35 (d, J=8.5 Hz, 2H), 6.53 (d, J=8.5 Hz, 1H), 4.90 (s, 2H), 4.43 (s, 2H), 3.65-3.61 (m, 2H), 3.46-3.39 (m, 2H), 2.83-2.78 (m, 5H), 2.48-2.43 (m, 2H); ESI MS m/z 382 [M+H]+.
