Potassium Carbonate → HCID 131732906, compound

Temperature

100 °C

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]+.

1. customin N,N-dimethylformamide (2 mL), was degassed with argon
2. customthe mixture was degassed again
3. temperaturethe reaction mixture was cooled to ambient temperature
4. additiondiluted with ethyl acetate (25 mL)
5. washwashed with water (10 mL)
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated in vacuo
8. customThe residue was purified by preparative TLC (90:9:1 methylene chloride/methanol/ammonium hydroxide)

ORD record

ord-eba5a07e83284fd19be3e9d0bf0d74c2

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09045468B2