反应详情

温度

25 °C

The crude cis-2-(2-cyclopropyl-ethylamino)-cycloheptanecarboxylic acid methyl ester (260.5 mg, 1.09 mmol) was mixed with (7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (prepared as described in Example 1j, 399 mg, 1.2 mmol) and dissolved in N,N-dimethylformamide (9 mL). N-Methylmorpholine (264 μL, 2.4 mmol) was added followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (230 mg, 1.2 mmol). The resulting mixture was shaken at 25° C. overnight. A 1.0 M aqueous hydrochloric acid solution (11 mL) was added (pH=2) and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine (40 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was further dried in vacuo for 5.5 h to afford the crude product, 2-{(2-cyclopropyl-ethyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cycloheptanecarboxylic acid methyl ester, containing 2-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetylamino]-cycloheptanecarboxylic acid methyl ester as a side product, as a brown oil. This crude product was directly used in the next step without further purification. LC-MS (ESI) calcd for C24H34N4O7S2 554.19, found 555.3 [M+H+] and LC-MS (ESI) calcd for C19H26N4O7S2 486.12, found 487.3 [M+H+]+.

1. extractionthe mixture was extracted with ethyl acetate (3×50 mL)
2. washThe combined organic layers were washed with brine (40 mL)
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was further dried in vacuo for 5.5 h