A compound and its use
A compound, selected technology, applied in the field of compounds
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Embodiment 1
[0245] Example 1: N-(4-chlorophenyl)-2-(3-((6-fluoroquinolin-4-yl)oxy)-8-azabicyclo[3.2.1]oct-8-yl ) The preparation synthetic steps of propionamide are as follows:
[0246]
[0247] Step 1: Preparation of tert-butyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate
[0248] At room temperature, TEA (30.4 g, 300.0 mmol) was added dropwise to a mixed solution of nortropinone hydrochloride (16.2 g, 100.0 mmol) and DCM (300 mL), and the temperature of the system was controlled below 30°C. After the addition, add (Boc) in batches to the reaction system 2 O (24.0 g, 110.0 mmol), after the addition was complete, the reaction system was stirred at room temperature for 6 h. TLC shows that after the raw material reaction is completed, the reaction solution is once saturated with 1M dilute hydrochloric acid 2 CO 3 aqueous solution and saturated brine. Anhydrous Na for organic phase 2 SO 4 Drying and concentration under reduced pressure gave 22.1 g (yield: 98%) of the target compou...
Embodiment 2
[0263] Example 2: Endo-R-N-(4-chlorophenyl)-2-((1R, 3R, 5S)-3-((6-fluoroquinolin-4-yl)oxy)-8-aza The preparation of bicyclo[3.2.1]oct-8-yl)propionamide
[0264] The synthesis steps are as follows:
[0265]
[0266] Note: The synthesis method of the three isomers of endo-S (Example 62), exo-R (Example 63), and Exo-S (Example 64) is consistent with Example 2.
[0267] Step 1: Preparation of endo-4-(((1R,3R,5S)-8-azabicyclo[3.2.1]oct-3-yl)oxy)-6-fluoroquinoline
[0268] 3-((6-fluoroquinolin-4-yl)oxy)-8-azabicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (3.7g, 10.0mmol) in 50mL 4M HCl / EA solution was stirred at room temperature for 6h. TLC showed that after the completion of the reaction, the reaction system was directly concentrated under reduced pressure, and the obtained solid was dissolved in 50 mL of water, and the pH value was adjusted to alkaline with NaOH. The resulting system was extracted with EA (50mL x 5), the organic phase was backwashed once with satu...
Embodiment 3
[0277] Example 3: N-(4-chlorophenyl)-2-(3-((6-fluoroquinolin-4-yl)amino)-8-azabicyclo[3.2.1]oct-8-yl) The preparation synthetic steps of propionamide are as follows:
[0278]
[0279] Step 1: Preparation of tert-butyl 3-((6-fluoroquinolin-4-yl)amino)-8-azabicyclo[3.2.1]octane-8-carboxylate
[0280] Under nitrogen protection, tert-butyl 3-amino-8-azabicyclo[3.2.1]octane-8-carboxylate (2.3g, 10.2mmol) and 4-chloro-6-fluoroquinoline (1.8g, 9.9 mmol) in 30 mL DMSO solution was added CuI (0.2 g, 1.0 mol). After the addition was complete, the reaction mixture was stirred at 100° C. for 6 h under nitrogen protection. The reaction system was poured into 200 mL of water and extracted with EA (10 mL x 3). The organic phase was washed with saturated brine, anhydrous Na 2 SO 4 After sufficient drying and concentration under reduced pressure, the residue was purified by column chromatography (PE:EA = 1:1) to obtain 1.1 g (yield: 30%) of the target compound as a yellow solid.
[02...
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