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Synthesis method of penta-substituted 2-amino-2-pyrroline derivative

A synthetic method, pyrroline technology, applied in the direction of organic chemistry, can solve the problems of limited flexibility in substituent transformation, complicated operation, difficult preparation of raw materials, etc., and achieve the effect of avoiding high prices

Active Publication Date: 2017-11-24
SHAANXI NORMAL UNIV
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

The above methods represent the research progress of multi-substituted 2-amino-2-pyrrolines, but there are some shortcomings in different degrees, such as some raw materials are not easy to prepare, and some need to use transition metals as catalysts and high-temperature reflux or low-temperature reactions. Higher requirements increase the cost of synthesis; some methods have certain limitations in the selection of functional groups, and the flexibility of substituent transformation is limited; some require multi-step reactions and complex operations

Method used

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  • Synthesis method of penta-substituted 2-amino-2-pyrroline derivative
  • Synthesis method of penta-substituted 2-amino-2-pyrroline derivative
  • Synthesis method of penta-substituted 2-amino-2-pyrroline derivative

Examples

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Embodiment 1

[0023] Taking the synthesis of 1-p-toluenesulfonylamino-2-amino-3-cyano-4-phenyl-5-ethoxyformyl 2-pyrroline with the following structural formula as an example, the specific synthesis method is as follows:

[0024]

[0025] Add 0.425g (1mmol) ethyl 3-phenyl-2-(4-methylbenzenesulfonylamino)-3-bromopropionate, 0.063mL (1mmol) malononitrile, 0.212g (1mmol) potassium phosphate, 5mL N,N-dimethylformamide, stirred and reacted at 50°C for 1 hour, then added 25mL ethyl acetate, washed three times with saturated brine (25mL each time), and then water Wash three times (25 mL each time), dry the organic phase with anhydrous sodium sulfate, filter to remove the desiccant, and concentrate under reduced pressure. as the eluent), recrystallized from absolute ethanol to obtain 1-p-toluenesulfonylamino-2-amino-3-cyano-4-phenyl-5-ethoxyformyl-2-pyrroline as a white crystalline solid , the yield is 86%, the melting point is 200-202°C, and the structural characterization data are as follows: ...

Embodiment 2

[0030] Taking 1-p-toluenesulfonylamino-2-amino-3-cyano-4-(4-methylphenyl)-5-ethoxyformyl-2-pyrroline with the following synthetic structural formula as an example, the specific synthetic method as follows:

[0031]

[0032] In Example 1, the 3-phenyl-2-(4-methylbenzenesulfonylamino)-3-bromopropionic acid ethyl ester was used with equimolar 3-(4-methylphenyl)-2- (4-methylbenzenesulfonylamino)-3-ethyl bromopropionate was replaced, the reaction time was shortened to 50 minutes, other steps were the same as in Example 1, and white crystalline solid 1-p-toluenesulfonylamino-2- Amino-3-cyano-4-(4-methylphenyl)-5-ethoxyformyl-2-pyrroline, the yield is 57%, the melting point is 184-185°C, and the structural characterization data are as follows:

[0033] 1 H NMR (400MHz, DMSO-d 6 )δ=7.91(d,J=8.4Hz,2H),7.52(d,J=8.0Hz,2H),7.13-7.11(m,2H),7.03-7.01(m,4H),4.99(d,J =11.2Hz,1H),4.48(d,J=11.2Hz,1H),3.66-3.58(m,1H),3.45-3.32(m,1H),2.45(s,3H),2.26(s,3H) ,0.73(t,J=7.2Hz,3H).

[0034] 1...

Embodiment 3

[0037] Taking 1-p-toluenesulfonylamino-2-amino-3-cyano-4-(2-methylphenyl)-5-ethoxyformyl-2-pyrroline with the following synthetic structural formula as an example, the specific synthetic method as follows:

[0038]

[0039] In Example 1, the 3-phenyl-2-(4-methylbenzenesulfonylamino)-3-bromopropionic acid ethyl ester was used with equimolar 3-(2-methylphenyl)-2- (4-methylbenzenesulfonylamino)-3-ethyl bromopropionate was replaced, the reaction time was extended to 1.5 hours, other steps were the same as in Example 1, and white crystalline solid 1-p-toluenesulfonylamino-2- Amino-3-cyano-4-(2-methylphenyl)-5-ethoxyformyl-2-pyrroline, the yield is 69%, the melting point is 159-161°C, and the structural characterization data are as follows:

[0040] 1 H NMR (400MHz, DMSO-d 6 )δ=7.96(d, J=8.4Hz, 2H), 7.52(d, J=8.4Hz, 2H), 7.17-7.14(m, 3H), 7.09-7.06(m, 1H), 7.02(s, 2H ),5.12(d,J=11.2Hz,1H),4.72(d,J=11.2Hz,1H),3.61-3.53(m,1H),3.31~3.23(m,1H),2.45(s,3H) ,2.29(s,3H),0.71(t,J=7.2...

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Abstract

The invention discloses a synthesis method of a penta-substituted 2-amino-2-pyrroline derivative. In an organic medium with higher polarity, the aryl propionate of ortho-amino halide and malononitrile are enabled to generate a nucleophilic substitution reaction and a nucleophilic ring closing reaction once under the action of an alkali; the penta-substituted 2-amino-2-pyrroline derivative is obtained in one step. According to the synthesis method, a common alkali which is low in cost is adopted as an accelerant; the cost is effectively decreased; further, no matter that the aryl propionate of the ortho-amino halide is the aryl propionate of alpha-amino-beta halide or alpha-halide-beta-amino, the amino in a synthesized product is always located at the 2-site of the ring of pyrroline; carbon-carbon double bonds in the pyrroline are both located at a 2-site and 3-site; the 2-amino-2-pyrroline derivative has high regioselectivity. The selection of a substituent group in the 2-amino-2-pyrroline derivative synthesized by the synthesis method has higher flexibility; the 2- site amino and the 3-site cyano can generate a 4+1 or 4+2 cyclization reaction; the 2-amino-2-pyrroline derivative can be used for the fields of the synthesis of fused heterocyclic compounds, natural antibiotics and anti-cancer drugs and the research of the structural modification of natural products.

Description

technical field [0001] The invention belongs to the technical field of synthesis of pentasubstituted 2-amino-2-pyrroline derivatives, and specifically relates to the synthesis of pentasubstituted 2-amino-2-pyrrole by one-step reaction of an aryl propionate of an ortho-amino halide and malononitrile The method of morphine derivatives. Background technique [0002] There are many kinds of nitrogen-containing heterocyclic compounds, including three-membered nitrogen-containing heterocyclic compounds, five-membered nitrogen-containing heterocyclic compounds, and six-membered nitrogen-containing heterocyclic compounds. Pyrroline derivatives are an important class of five-membered nitrogen-containing heterocyclic compounds, which can be divided into 1-pyrroline, 2-pyrroline and 3-pyrroline from the structure. These pyrroline derivatives are widely used in alkaloids, Synthesis of active pharmaceutical compounds and optoelectronic materials. At the same time, compounds with pyrrol...

Claims

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Application Information

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IPC IPC(8): C07D207/48
CPCC07D207/48
Inventor 陈战国康梦康楠
Owner SHAANXI NORMAL UNIV
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