3-substituted 1,2,3.4-tetrahydro-quinazine derivative, its synthesis and use

A technology of tetrahydroquinoline and derivatives, which is applied in the field of 3-substituted 1, can solve the problems of limited synthesis conditions of quinoline derivatives, difficulty in preparing 3-aryl groups, and difficult operation, so as to avoid hydrogenation and reduction response, treatment of cerebral ischemia, effects of mild conditions

Inactive Publication Date: 2006-08-16
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These reduction methods have harsh conditions and are not easy to operate, and the diversity of quinoline derivatives is greatly limited by the synthesis conditi

Method used

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  • 3-substituted 1,2,3.4-tetrahydro-quinazine derivative, its synthesis and use
  • 3-substituted 1,2,3.4-tetrahydro-quinazine derivative, its synthesis and use
  • 3-substituted 1,2,3.4-tetrahydro-quinazine derivative, its synthesis and use

Examples

Experimental program
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Example Embodiment

[0024] The synthesis method includes: under alkaline conditions, substituted o-nitrobenzaldehyde or o-aminobenzaldehyde and arylacetonitrile derivatives are condensed to form an acrylonitrile compound of structural formula A; the acrylonitrile compound of structural formula A undergoes double bond The reduction reaction is reduced to a propionitrile compound of structural formula B; then the ring is closed under catalytic hydrogenation conditions to generate a 3-substituted 1,2,3,4-tetrahydroquinoline derivative.

[0025] Among them, in the condensation of substituted o-nitrobenzaldehyde or o-aminobenzaldehyde and arylacetonitrile derivatives to form an acrylonitrile compound of structural formula A, the base used can be an inorganic base, such as potassium carbonate; or an organic base, Such as organic amines, sodium alkoxide or potassium alkoxide. The amount of base used is a molar ratio of 10%-100% of any reactant.

[0026] The acrylonitrile compound of structural formula A is ...

Example Embodiment

[0030] Example 1

[0031] Preparation of Acrylonitrile Compounds of Structural Formula A

[0032] (1) Preparation of (Z)-3-(2-nitrophenyl)-2-phenylacrylonitrile (A-1)

[0033] Dissolve 0.23g (10mmol) of sodium in 50mL of absolute ethanol, add 15.12g (100mmol) of 2-nitrobenzaldehyde and 11.71g (100mmol) of benzylacetonitrile under stirring, stir at room temperature for 4h, filter, and wash with absolute ethanol. Bright yellow solid 23.00g, yield 92.0%.

[0034] 1 HNMR(300MHz, CDCl 3 )δ7.42-7.53(m, 3H), 7.64(t, J=8.2, 1H), 7.73(dd, J=1.7, 8.1, 2H), 7.80(t, J=7.6, 1H), 7.95(d , J=7.6, 1H), 8.06 (s, 1H), 8.26 (d, J=8.3, 1H); MS (EI): m / e (%) 250 (16M + ), 119(100), 92(84).

[0035] (2) Preparation of (Z)-2-(4-methoxyphenyl)-3-(2-nitrophenyl)-acrylonitrile (A-2)

[0036] 2-Nitrobenzaldehyde and 4-methoxybenzeneacetonitrile were carried out according to the method described in Example 1.(1) to obtain compound A-2 with a yield of 74.2%.

[0037] 1 HNMR(300MHz, CDCl 3 )δ3.87(s, 3H), 6.99(...

Example Embodiment

[0095] Example 2

[0096] Preparation of propionitrile compounds of structural formula B

[0097] (1) Preparation of 3-(2-nitrophenyl)-2-phenylpropionitrile (B-1)

[0098] Dissolve 5.00g (20mmol) (Z)-3-(2-nitrophenyl)-2-phenyl-acrylonitrile in 20mL anhydrous tetrahydrofuran, add 1.13g (30mmol) sodium borohydride in batches under ice water bath Stir at room temperature; after TLC monitors that there is no raw material, quench with 1mol / L HCl, concentrate under reduced pressure to remove tetrahydrofuran, then extract with ethyl acetate, wash with saturated sodium chloride solution, dry the organic phase with anhydrous magnesium sulfate, filter, and concentrate under reduced pressure to give yellow The solid is 4.80 g, and the yield is 92.0%. No purification is required for the next reaction.

[0099] 1 HNMR(300MHz, CDCl 3 )δ3.22 (dd, J=10.3, 13.3, 1H), 3.54 (dd, J=5.2, 13.1, 1H), 4.39 (dd, J=5.1, 10.8, 1H), 7.32-7.53 (m, 7H) , 7.60-7.66 (m, 1H), 8.08 (d, J=8.1, 1H); MS (EI): m / e (%)...

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Abstract

A 3-substituted 1, 2, 3, 4-tetrahydro-quinoline derivative, its synthesis and use are disclosed. The procedure is carried out by condensing substituted-o-nitrobenzaldehyde or o-aminobenzaldehyde with aryl-acetonitrile derivative, reducing by double bond and obtaining 3-substituted 1, 2, 3, 4-tetraquinazine derivate by loop closing under the condition of catalytic hydrogenation. It can be used for cerebral local ischemia, suppressive vasorelaxation, antiarrhythmic and antineoplastic activities. It is simple, has gentle reactive condition and more output.

Description

technical field [0001] The present invention relates to 3-substituted 1,2,3,4-tetrahydroquinoline derivatives and their synthesis methods and applications, more specifically, to 1,2,3,4-tetrahydroquinoline derivatives substituted by aryl at the 3-position Hydroquinoline derivatives and their synthesis methods and uses. Background technique [0002] Tetrahydroquinoline and tetrahydroisoquinoline widely exist in nature, 1,2,3,4-tetrahydroquinoline compounds have the activities of inhibiting vasodilation, antiarrhythmia and antitumor, and also have the effect of immunosuppressant , is also a more characteristic dye intermediate. [0003] Many tetrahydroquinoline derivatives are considered to be strong affinity ligands at the glycine position of the DMAD receptor, and are also a convenient factor for the transmission of norepinephrine, and they are also inotropic sensitizers that do not affect the operation of calcium ions in cells, so It is a potential drug for treating cereb...

Claims

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Application Information

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IPC IPC(8): C07D215/02C07D491/04A61K31/47A61K31/4741A61P9/10
Inventor 陈五红贺茜杨春皓谢毓元
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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