Method for preparing polysubstituted isoquinoline and heterocyclic pyridine derivants
A compound and cyclization reaction technology, applied in the direction of organic chemistry, can solve the problems that cannot be applied to the synthesis of isoquinoline derivatives, and achieve high catalytic activity and selectivity, simple reaction operation, and strong universality
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[0052] Wherein, the preparation method of the compound shown in formula II is as follows: the compound shown in formula a, the compound shown in formula b, PdCl 2 (PPh 3 ) 2 , CuI, tetrahydrofuran and triethylamine are mixed in an inert atmosphere to react, and the compound shown in formula II is obtained after the reaction is completed. Compound shown in formula a, compound shown in formula b, PdCl 2 (PPh 3 ) 2 , CuI, tetrahydrofuran and triethylamine are 1mmol: 11mmol: 0.01mmol: 0.02mmol: 2mL: 1mL; in the reaction step, the temperature is 60°C and the time is 5 hours; the method also includes: After completion, the mobile phase was a mixture of ethyl acetate and petroleum ether with a volume ratio of 2:100 for column chromatography to obtain the target product.
[0053]
[0054] Formula a Formula b
[0055] In formula a and formula b, R 1 , R 2 and R 3 The definition is the same as before.
Embodiment 1
[0057] Weigh CuSO 4 Add 16mg (0.1mmol), 206mg (1mmol) of o-phenylethynyl benzaldehyde, 120mg (2mmol) of urea and 2mL toluene into a 25-mL glass reaction tube with a cover, replace the air in the reaction tube with nitrogen, and then seal the reaction tube , put the reaction tube in an oil bath and heat it to 120°C, stir and keep warm for 12 hours, then cool to room temperature to obtain the target product 3-phenylisoquinoline provided by the present invention. Reaction result: the isolated target product 3-phenylisoquinoline was weighed, and the isolated yield of the product was calculated to be 79%. figure 1 with figure 2 The hydrogen spectrum and carbon spectrum of the target product 3-phenylisoquinoline prepared in this example are shown respectively. It can be seen from the figure that the compound has a correct structure and is the target product.
Embodiment 2
[0059] Weigh CuSO 4 16mg (0.1mmol), o-ethynyl benzaldehyde 130mg (1mmol), urea 120mg (2mmol) and 2mL toluene were added in a 25-mL glass reaction tube with a cover, the air in the reaction tube was replaced with nitrogen, and then the reaction tube was sealed. Put the reaction tube in an oil bath and heat to 120°C, stir and keep warm for 12 hours, then cool to room temperature to obtain the target product isoquinoline provided by the present invention. Reaction result: the isolated target product isoquinoline was weighed, and the isolated yield of the product was calculated to be 23%. image 3 with Figure 4 The hydrogen spectrum and carbon spectrum of the target product isoquinoline prepared in this example are respectively, as can be seen from the figure, the compound has a correct structure and is the target product.
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