Spiropyridino[2,1-a]isoquinoline compound and synthesizing method thereof

A technology of spirocyclic pyridine and synthesis method, which is applied in biocides, organic chemistry, drug combination, etc., can solve the problems of small expansion range of substrates, harsh reaction conditions, and difficult acquisition of raw materials, etc., to achieve large expansion range of substrates, The effect of high diastereoselectivity and easy availability of raw materials

Inactive Publication Date: 2018-05-18
YANGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Currently spiropyrido[2,1- a ] The synthesis of isoquinoline compounds has not been reported in the literature, and the existing reports only involve the synthesis of partly combined ring structu

Method used

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  • Spiropyridino[2,1-a]isoquinoline compound and synthesizing method thereof
  • Spiropyridino[2,1-a]isoquinoline compound and synthesizing method thereof
  • Spiropyridino[2,1-a]isoquinoline compound and synthesizing method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1, preparation of 1,3-dioxo-2'-phenyl-1,3-dihydro-2' with the following structural formula H , 11b' H -Spiro[indene-2,1'-pyrido[2,1- a ]isoquinoline]-3',4'-dicarboxylic acid dimethyl ester, its reaction formula is as follows:

[0027]

[0028] Preparation:

[0029]Dissolve 0.1460 g (1.0 mmol) of 1,3-indandione in 15 mL of absolute ethanol, and add 0.0530 g (0.5 mmol) of benzaldehyde and 1.0119 g (10 mmol) of triethylamine dropwise under stirring, at 20°C The reaction was carried out for 10 hours, and suction filtration was completed after the reaction to obtain 1,3-indandione benzaldehyde.

[0030] Add 0.2340 g (1.0 mmol) 1,3-indanedionate benzaldehyde, 0.1420 g (1.0 mmol) dimethyl butynedioate and 10 mL dry acetonitrile into a round bottom flask, and add 0.1290 g ( 1.0mmol) isoquinoline, be warming up to 30 ℃, stir 0.5 hour, analyze by thin-layer chromatography, after reaction finishes, stop reaction, solvent is concentrated and evaporated on rotary evap...

Embodiment 2

[0036] Example 2, preparation of 1,3-dioxo-2'-(p-tolyl)-1,3-dihydro-2' with the following structural formula H ,11b' H -Spiro[indene-2,1'-pyrido[2,1- a ]isoquinoline]-3',4'-dicarboxylic acid dimethyl ester:

[0037]

[0038] specific method:

[0039] Dissolve 0.1460 g (1.0 mmol) of 1,3-indandione in 15 mL of absolute ethanol, and add dropwise 0.0600 g (0.5 mmol) of p-tolualdehyde and 1.5178 g (15 mmol) of triethylamine under stirring, at 25 The reaction was carried out under the condition of ℃ for 10 hours, and after the reaction was completed, it was filtered with suction to obtain 1,3-indandione acetal p-tolualdehyde.

[0040] Add 0.2340 g (1.0 mmol) 1,3-indanedione p-methylbenzaldehyde, 0.0710 g (0.5 mmol) dimethyl butyndioate and 10 mL of dry acetonitrile into a round bottom flask, and add them under stirring at room temperature 0.0645 g (0.5mmol) isoquinoline, be warming up to 45 ℃, stir 1 hour, analyze by thin-layer chromatography, after reaction finishes, stop re...

Embodiment 3

[0046] Example 3, preparation of 2'-(2-methoxyphenyl)-1,3-dioxo-1,3-dihydro-2' with the following structural formula H ,11b' H -Spiro[indene-2,1'-pyrido[2,1- a ]isoquinoline]-3',4'-dicarboxylic acid dimethyl ester:

[0047]

[0048] specific method:

[0049] 0.1460 g (1.0 mmol) of 1,3-indandione was dissolved in 15 mL of absolute ethanol, and 0.1360 g (1.0 mmol) of o-methoxybenzaldehyde and 1.5178 g (15 mmol) of triethylamine were added dropwise under stirring. The reaction was carried out at 30° C. for 11 hours. After the reaction was completed, it was filtered with suction to obtain 1,3-indandione acetal-o-methoxybenzaldehyde.

[0050]Add 0.2340 g (1.0 mmol) of 1,3-indanedione acetal-o-methoxybenzaldehyde, 0.0710 g (0.5 mmol) of dimethyl butyndioate and 10 mL of dry acetonitrile into a round bottom flask, and stir at room temperature Add 0.1290 g (1.0 mmol) isoquinoline, be warming up to 45 ℃, stir 2 hours, analyze by thin-layer chromatography, after reaction finishes...

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Abstract

The invention discloses a spiropyridino[2,1-a]isoquinoline compound and a synthesizing method thereof, and belongs to the technical field of organic synthesis. In acetonitrile, a 1,3-indandione condensed aromatic aldehyde compound, dimethyl acetylenedicarboxylate and isoquinoline are mixed to have a [4+2] cycloaddition reaction for 0.5-5 h at 30-70 DEG C, and silica gel column chromatography is conducted with a mixed solvent of ethyl acetate and petroleum ether after the addition reaction ends to obtain the spiropyridino[2,1-a]isoquinoline compound. The compound is light yellow solid, has themelting point of about 210-240 DEG C, can be easily dissolved in an organic solvent, and can be applied in medicines and pesticides.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis. Background technique [0002] Recent studies have shown that isoquinoline derivatives have certain activity as angiotensin-converting enzyme inhibitors. (Markmee, S.; Ruchirawat, S.; Prachyawarakorn, V.; Lngkaninan, K.; Khorana, N. Isoquinoline derivatives as potential acetylcholinesterase inhibitors. Bioorg. Med. Chem. Lett. 2006, 16, 2170-2172). In 2006, Trotter et al. designed and synthesized a series of 3-cyano substituted isoquinoline derivatives for the treatment of atrial fibrillation. (Trotter, B. W.; Nanda, K.K.; Kett, N. R.; Regan, C. P.; Lynch, J. J.; Stump, G. L.; Kiss, L.; Wang, J.; Spencer, R. H.; Kane, S. A.; White, R. B.; Zhang, R. .; Anderson, K. D.; Liverton, N. J.; McIntyre, C. J.; Beshore, D. C.; Hartman, G. D.; Dinsmore, C.J. Design and Synthesis of Novel Isoquinoline-3-nitrites as Orally Bioavailable Kv1.5 Antagonists for the Treatment of Atrial Fibrillation. ...

Claims

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Application Information

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IPC IPC(8): C07D471/10A01P3/00A01P1/00A61P31/04A61P33/02A61P21/02
Inventor 韩莹张媛媛颜朝国孙晶
Owner YANGZHOU UNIV
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