Synthetic method of penta-substituted 2-amino pyrrole derivatives

A technology of aminopyrrole and synthesis method, which is applied in the direction of organic chemistry, can solve the problems of excessive heavy metal residues, increased equipment requirements, increased costs, etc., and achieves high regioselectivity, reduced synthesis costs, and low prices.

Inactive Publication Date: 2016-10-12
SHAANXI NORMAL UNIV
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Problems solved by technology

There are some shortcomings in the above methods in varying degrees. If some methods use transition metals as catalysts, excessive heavy metal residues in drug synthesis are difficult problems to solve in drug synthesis; Increase the cost of synthesis; some have to be carried out at higher temperature, even at reflux temperature, which increases the requirements for equipment

Method used

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  • Synthetic method of penta-substituted 2-amino pyrrole derivatives
  • Synthetic method of penta-substituted 2-amino pyrrole derivatives
  • Synthetic method of penta-substituted 2-amino pyrrole derivatives

Examples

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Comparison scheme
Effect test

Embodiment 1

[0020] Taking the synthesis of 1-p-toluenesulfonyl-2-amino-3-cyano-4-phenyl-5-benzoylpyrrole with the following structural formula as an example, the specific synthesis method is as follows:

[0021]

[0022] Add 0.457g (1mmol) 1-phenyl-3-phenyl-2-(4-methylbenzenesulfonylamino)-3-bromoacetone-1, 0.066g (1mmol) propylene glycol to a 50mL round bottom flask successively Nitrile, 0.106g (1mmol) sodium carbonate, 5mL methanol, magnetic stirring reaction at 50°C for 8 hours, then add 25mL ethyl acetate, wash with saturated brine three times (each 25mL), and then wash with water three times (each 25mL) , the organic phase was dried overnight with anhydrous sodium sulfate, filtered to remove the desiccant, concentrated under reduced pressure, and the crude product was subjected to silica gel column chromatography (with petroleum ether and ethyl acetate volume ratio of 5:1 mixed solution as eluent), 1-p-toluenesulfonyl-2-amino-3-cyano-4-phenyl-5-benzoylpyrrole was obtained in a yie...

Embodiment 2

[0027] Taking the synthesis of 1-p-toluenesulfonyl-2-amino-3-cyano-4-(4-chlorophenyl)-5-benzoylpyrrole as an example, the specific synthesis method is as follows:

[0028]

[0029] In Example 1, the 1-phenyl-3-phenyl-2-(4-methylbenzenesulfonylamino)-3-bromoacetone-1 was used with equimolar 1-phenyl-3-(4 -Chlorophenyl)-2-(4-methylbenzenesulfonylamino)-3-bromoacetone-1 was replaced, the reaction time was extended to 14 hours, and other steps were the same as in Example 1 to obtain yellow solid 1-p-toluenesulfonate Acyl-2-amino-3-cyano-4-(4-chlorophenyl)-5-benzoylpyrrole has a yield of 70%, a melting point of 198.8-199.9°C, and structural characterization data as follows:

[0030] 1 H NMR (400MHz, DMSO-d 6 )δ: 7.47(m, 7H), 7.27(dd, J=14.2, 6.5Hz, 4H), 7.19(d, J=8.4Hz, 2H), 7.11(d, J=8.4Hz, 2H), 2.42( s, 3H).

[0031] 13 C NMR (100MHz, DMSO-d 6 )δ: 190.0, 150.8, 146.7, 136.2, 133.4, 133.2, 133.0(2), 130.3(2), 129.0(2), 128.3(2), 128.3(2), 127.2(2), 126.9(2), 126.7(2), 125....

Embodiment 3

[0034] Taking the synthesis of 1-p-toluenesulfonyl-2-amino-3-cyano-4-(4-bromophenyl)-5-benzoylpyrrole as an example with the following structural formula, the specific synthesis method is as follows:

[0035]

[0036] In Example 1, the 1-phenyl-3-phenyl-2-(4-methylbenzenesulfonylamino)-3-bromoacetone-1 was used with equimolar 1-phenyl-3-(4 -Bromophenyl)-2-(4-methylbenzenesulfonylamino)-3-bromoacetone-1 was replaced, the reaction time was extended to 9 hours, and other steps were the same as in Example 1 to obtain yellow solid 1-p-toluenesulfonate Acyl-2-amino-3-cyano-4-(4-bromophenyl)-5-benzoylpyrrole has a yield of 84%, a melting point of 201.8-202.8°C, and structural characterization data as follows:

[0037] 1 H NMR (400MHz, DMSO-d 6 )δ: 7.48 (m, 7H), 7.37~7.22 (m, 6H), 7.06 (dd, J=8.2, 2.4Hz, 2H), 2.40 (s, 3H).

[0038] 13 C NMR (100MHz, DMSO-d 6 )δ: 190.0, 150.8, 146.6, 136.2, 133.2, 130.3(2), 130.1(4), 129.0(2), 128.7(2), 128.3(2), 126.9(2), 126.8, 125.3, 122.1(2...

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Abstract

The invention discloses a synthetic method of penta-substituted 2-amino pyrrole derivatives, wherein the method comprises that in an organic medium with relatively large polarity, arone of o-amino halogen and malononitrile are subjected to a reaction in one step under the action of an alkali, and the penta-substituted 2-amino pyrrole derivatives can be obtained. Compared with a traditional method, the method adopts the low-price ordinary alkali as an accelerant, effectively reduces the cost, and has the advantages of simple synthetic steps and high reaction yield; especially in construction of a drug with a pyrrole ring, with use of the method, the problem that the residual amount of heavy metals in the drug exceeds standards due to use of the heavy metals for catalysis can be avoided. In addition, no matter arone of o-amino halogen is alpha-amino-beta-halogen arone or alpha-halogen-beta-amino arone, amino in the synthetic products is located at 2-site of the pyrrole ring and has high region selectivity. The synthetic penta-substituted 2-amino pyrrole derivatives can be used in the fields of synthesis of fused heterocyclic compounds, natural antibiotics and anticancer drugs and modification research of natural product structures.

Description

technical field [0001] The invention belongs to the technical field of synthesis of pentasubstituted 2-aminopyrrole derivatives, and in particular relates to a method for synthesizing pentasubstituted 2-aminopyrrole by one-step reaction of aryl ketone with an ortho-amino halide and malononitrile. Background technique [0002] Pyrrole and its derivatives are a very important class of five-membered heterocyclic compounds. Pyrrole was first discovered in the 1930s. Since then, the biological activity and pharmacological effects of pyrrole and its derivatives have attracted widespread attention. Today, pyrrole and its derivatives have been widely used in the fields of medicine, pesticide, food, biology, material science and polymer chemistry. Due to the importance of pyrrole and its derivatives, their synthetic methods have been intensively studied. The 2-aminopyrrole structural unit is a part of many compounds with strong biological activity, and has been recognized as the st...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D207/48
CPCC07D207/48
Inventor 陈战国李亚男惠文萍康梦
Owner SHAANXI NORMAL UNIV
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