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3, 3'-disubstituted 3-pyrrole oxoindole compound and asymmetric synthetic method thereof

A technology of indole compound and synthesis method, which is applied in the field of 3-pyrrole oxindole compound and its asymmetric synthesis, achieving the effects of mild reaction conditions, simple operation and high stereoselectivity

Active Publication Date: 2014-10-08
CHENGDU LIKAI CHIRAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the 3-monosubstituted oxindole substituted by nitrogen-containing heteroatom functional group at the C3 position is used as a nucleophile to participate in an asymmetric reaction for the construction of chiral 3,3'-disubstituted 3-aminoindole compounds There are very few reports
Especially, the reaction of 3-pyrrole oxindole as a nucleophile to construct 3,3'-disubstituted 3-pyrrole oxindole has not been reported yet.

Method used

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  • 3, 3'-disubstituted 3-pyrrole oxoindole compound and asymmetric synthetic method thereof
  • 3, 3'-disubstituted 3-pyrrole oxoindole compound and asymmetric synthetic method thereof
  • 3, 3'-disubstituted 3-pyrrole oxoindole compound and asymmetric synthetic method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Embodiment 1 The compound shown in the following structural formula 1a and asymmetric synthesis

[0038]

[0039] Synthetic method: In a hard reaction tube, 1-methyl-3-(1 H -Pyrrol-1-yl)indolin-2-one (21.2 mg, 0.1 mmol), catalyst 3-((3,5-bis(trifluoromethyl)phenyl)amino)-4-((( S)-(6-methoxyquinuclidin-4-yl)((1S,2S,4S,5R)-5-vinylquinuclidin-2-yl)methyl)amino)cyclobut-3-ene -1,2-dione (3.2 mg, 0.005 mmol) and ( E )-(2-nitrovinyl)benzene (22.4 mg, 0.15 mmol) was dissolved in 2 mL of freshly distilled dichloromethane, and the mixture was o The reaction was stirred at C for 54 h. After the reaction was monitored by TLC, the mixture was directly separated and purified by column chromatography (the mobile phase was petroleum ether:ethyl acetate=10:1~3:1) to obtain a white solid with a yield of 97%. After structural identification, the structure of the solid was For the above-mentioned compound 1a, the specific data of its structural identification are:

[0040] The...

Embodiment 2

[0041] Embodiment 2: the compound of structural formula as shown below 2a and asymmetric synthesis

[0042]

[0043] Synthetic method: In a hard reaction tube, 1-methyl-3-(1 H -pyrrol-1-yl)indolin-2-one (21.2 mg, 0.1 mmol), (DHQD) 2 PHAL (7.8 mg, 0.01 mmol) and diethyl azodicarboxylate (26.1 mg, 0.15 mmol) were dissolved in 2 mL of freshly distilled chlorobenzene, and the mixture was stirred at -20°C for 60 h. After the reaction was monitored by TLC, the mixture was directly separated and purified by column chromatography (the mobile phase was petroleum ether: ethyl acetate=10:1~2:1) to obtain a white solid with a yield of 98%; through structural identification, the structure of the solid For the above-mentioned compound 2a, the specific data of its structural identification are:

[0044] The ee value is 80%. [α] D 20 = +113.6 ( c 1.57, CHCl 3 ); mp 181.3-182.7 oC; the ee was determined by HPLC (Chiralpak OD-H, EtOH / hexane = 5 / 95, flow rate 1.0 mL / min, lambda = ...

Embodiment 3

[0045] Embodiment 3: the compound of structural formula as shown below 3a and asymmetric synthesis

[0046]

[0047] Synthetic method: In a hard reaction tube, 1-methyl-3-(1 H -Pyrrol-1-yl)indolin-2-one (21.2 mg, 0.1 mmol), catalyst 1-(3,5-bis(trifluoromethyl)phenyl)-3-((1S,2S) -2-(Dimethylamino)cyclohexyl)thiourea (8.3 mg, 0.02 mmol) and 1-(p-methylphenyl)-1 H -Pyrrole-2,5-dione (28.1 mg, 0.15 mmol) was dissolved in 2 mL of freshly distilled dichloroethane, and the mixture was stirred at room temperature for 6 days. After the reaction was monitored by TLC, the mixture was directly separated and purified by column chromatography (the mobile phase was petroleum ether:ethyl acetate=10:1~2:1) to obtain a white solid with a yield of 56%; after structural identification, the structure of the solid For the above-mentioned compound 1a, the specific data of its structural identification are:

[0048] The dr value is 85:15, and the ee value is 93%. [α] D 20 = -232.4 ( c 1....

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Abstract

The invention discloses a 3, 3'-disubstituted 3-pyrrole oxoindole compound and an asymmetric synthetic method thereof and belongs to the fields of organic chemistry and medicines. The structure of the compound takes the 3, 3'-disubstituted 3-pyrrole oxoindole compound as a framework, and the type of indole alkaloid is enriched so as to provide a sufficient compound source for screening pharmaceutical activity. Meanwhile, a synthetic method of the compound is provided. The asymmetric synthetic method comprises the following steps: dissolving 3-pyrrole oxoindole, an electrophilic reagent and a chiral catalyst in an organic solvent; carrying out a reaction at (-20)-25 DEG C; after reaction, separating and purifying to obtain the compound. The method is mild in reaction condition, easy in obtaining of raw materials and catalyst, free from metal residues, simple to operate, high in yield and further high in stereoselectivity.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a 3,3'-disubstituted 3-pyrrole oxindole compound and an asymmetric synthesis method thereof. Background technique [0002] 3,3'-disubstituted oxindole is the core skeleton of many natural products and drugs. Most of these natural molecules and drug molecules have been found to have good biological activity and are an important source for the development of new drugs. Among them, the 3,3'-disubstituted 3-aminooxindole skeleton is widely found in many natural alkaloids and compounds with pharmaceutical activity, so it is of great significance to construct such compounds through methodological research. [0003] At present, the reported asymmetric synthesis of 3,3'-disubstituted 3-aminoindole compounds is mainly through the asymmetric addition reaction of nucleophilic reagents to isatinimine, and the 3-monosubstituted oxindole Asymmetric amination and hydroxylation reacti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/04C07D403/14
CPCC07D403/04C07D403/14
Inventor 袁伟成崔宝东游勇周鸣强赵建强左键白玫张晓梅
Owner CHENGDU LIKAI CHIRAL TECH
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