Preparation method of heterocyclic compound and salt thereof
A technology for heterocyclic compounds and compounds, applied in the field of organic chemical synthesis, can solve problems such as unfavorable industrial production, cumbersome preparation routes, etc.
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Embodiment 1
[0146]
[0147] Weigh 10g of tetrahydropyran-4-cyano-4-carboxylic acid 1 into 50mL of N,N-dimethylformamide (DMF) and stir to dissolve, then gradually add 15mL of triethylamine, continue stirring for about 5min, Gradually add 40g diphenylphosphoryl azide (DPPA) dropwise. After the dropwise addition, stir the reaction at room temperature. After about 3 hours of reaction, TLC monitors the reaction and shows that the reaction conversion is complete. The prepared acyl azide compound is directly used for subsequent feeding without separation. , and then add 200mL of tert-butanol to the system, then gradually raise the temperature of the system to 110°C for reaction, the system will generate gas during the reaction, stop the reaction after about 8 hours of reaction, put the system on a rotary evaporator to spin off the system solvent, The remaining brown oily liquid was dissolved in ethyl acetate, washed once with saturated sodium bicarbonate solution, and then the organic phase w...
Embodiment 2
[0149]
[0150] Weigh 5g of Compound 2 and dissolve it in 100mL of methanol, then place the system in an ice bath to cool, gradually add 50mL of 6M hydrochloric acid solution dropwise, continue to stir for 2 hours after the addition, after the reaction, put the system in a rotary evaporator The solvent in the system was spun off to obtain a dark white solid powder, which was purified on a silica gel column to obtain 1.7 g of a yellow oil, namely compound 3, with a yield of 61%.
Embodiment 3
[0152]
[0153] Put 11g of compound 2 in 200mL of DMF and stir to dissolve, then place the system in an ice bath to cool, then add 4g of 60% sodium hydride solid in batches, after the addition, continue to stir the system for 10min, then gradually add 10g of methyl iodide , after the addition, the system continued to stir for 10 min under ice bath, then placed at room temperature to stir the reaction, TLC monitored the reaction until the conversion of raw materials was complete, then added 20 mL of saturated sodium sulfite solution to quench the reaction, filtered the quenched system, and collected the filtrate , then the system solvent was removed, the residue was dissolved in ethyl acetate, the insoluble matter was filtered off, the filtrate was collected, and washed once with saturated sodium bicarbonate, the ethyl acetate phase was collected, and dried with anhydrous sodium sulfate, and the dried acetic acid The ethyl ester phase was collected and the solvent was spun of...
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