Trans-3-indolyl-4-pyrroldiazepinecycloheptane-2,5-pyrrolidine-2,5-diketone compound and preparation method thereof
A technology of diazepines and compounds, applied in the field of pharmaceutical chemical synthesis
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Embodiment 1
[0034] The preparation of embodiment 1 intermediate 2-(1H-indol-7-yl) acetonitrile
[0035]
[0036] Add 7-formylindole (14.8g, 100mmol) and dry tetrahydrofuran (300ml) to a dry three-necked flask, then add lithium cyanide (350mg, 10mmol) and diethyl cyanophosphate (19.7ml, 130mmol) in sequence ), and stirred overnight at room temperature. After the reaction was detected by TLC, tert-butanol (10.0 ml, 100 mmol) was added and stirred for 30 minutes. At room temperature, the mixture was slowly added dropwise into 0.1M samarium iodide tetrahydrofuran solution (3.0L, 300mmol). After the addition was complete, stirring was continued for 30 minutes. The mixture was evaporated to dryness under reduced pressure, diluted with 2 liters of ethyl acetate, and then transferred to a separatory funnel, washed with 1N dilute hydrochloric acid (500ml×3), saturated sodium bicarbonate (500ml×2) and saturated saline (500ml) washing. Dry over anhydrous magnesium sulfate, filter and spin dry...
Embodiment 2
[0038] Preparation of Embodiment 2 Intermediate 2-(1H-indol-7-yl)ethylamine
[0039]
[0040] 2-(1H-indol-7-yl)acetonitrile (8.5g, 53.8mmol), Raney nickel (8.5g) and ammonia (3.6g) methanol ( 300ml) solution. Hydrogen gas was introduced to keep the pressure at 340 kPa (50 psi), and the mixture was stirred overnight at room temperature. After the reaction was completed, the Raney nickel was removed by filtration, evaporated to dryness under reduced pressure, and the residual solution was diluted with ethyl acetate / water (1:1, 500ml), stirred for 15 minutes and then separated. The organic layer was washed with saturated brine (100ml×2), dried over anhydrous sodium sulfate, filtered, and spin-dried to give 2-(1H-indol-7-yl)ethylamine (8.1g, 94%) as light yellow oil. LCMS (M+H)=161. Preparation of Example 3 Intermediate 2-(1H-indol-7-yl) ethyl tert-butyl carbamate
Embodiment 3
[0040] 2-(1H-indol-7-yl)acetonitrile (8.5g, 53.8mmol), Raney nickel (8.5g) and ammonia (3.6g) methanol ( 300ml) solution. Hydrogen gas was introduced to keep the pressure at 340 kPa (50 psi), and the mixture was stirred overnight at room temperature. After the reaction was completed, the Raney nickel was removed by filtration, evaporated to dryness under reduced pressure, and the residual solution was diluted with ethyl acetate / water (1:1, 500ml), stirred for 15 minutes and then separated. The organic layer was washed with saturated brine (100ml×2), dried over anhydrous sodium sulfate, filtered, and spin-dried to give 2-(1H-indol-7-yl)ethylamine (8.1g, 94%) as light yellow oil. LCMS (M+H)=161. Preparation of Example 3 Intermediate 2-(1H-indol-7-yl) ethyl tert-butyl carbamate
[0041]
[0042] Under nitrogen protection, 2-(1H-indol-7-yl)ethylamine (8.4g, 52.5mmol), dry tetrahydrofuran (200ml) and triethylamine (13.4 g, 131.2mmol), under stirring, a mixture of di-tert-but...
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