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Iminazole chiral organic micromolecule compound with bicyclo-structure and synthesizing method thereof

A technology of a small molecule compound and a synthesis method, which is applied in the field of imidazole chiral organic small molecule compounds and their synthesis, can solve the problems that have not yet been discovered, and achieve the effects of good application prospect, high catalytic activity and stereoselectivity.

Inactive Publication Date: 2010-03-24
SHANGHAI JIAO TONG UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The synthesis of this type of compound has also been reported in the literature (J.Hetercyclic Chem.1987,24,561), but it has not been found that this type of compound is applied to the literature report of asymmetric catalysis research.

Method used

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  • Iminazole chiral organic micromolecule compound with bicyclo-structure and synthesizing method thereof
  • Iminazole chiral organic micromolecule compound with bicyclo-structure and synthesizing method thereof
  • Iminazole chiral organic micromolecule compound with bicyclo-structure and synthesizing method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Preparation of 7-Hydroxy-6,7-dihydro-5H-pyrrole[1,2-α]imidazole

[0042] Add imidazole (50.0g, 0.734mol), glacial acetic acid (3.0ml, 0.051mol, 0.07eq) and solvent 1,4-dioxane (750ml) into a 1L three-necked flask, and stir to dissolve at room temperature. Then pour freshly steamed acrolein (63.0ml, 0.943mol, 1.3eq) in one go, and reflux for 48h. Then the volatile solvent was evaporated under reduced pressure, and the obtained solid crude product was separated by column chromatography (EtOAc / MeOH=3 / 1) to obtain 73.8 g of light yellow solid with a yield of 81%.

[0043] 1 H NMR (400MHz, CDCl 3 ): δ7.07(d, J=1.2Hz, 1H), 6.85(d, J=1.2Hz, 1H), 5.23(dd, J=3.2Hz, 7.2Hz, 1H), 4.24-4.16(m, 1H ), 3.98-3.98(m, 1H), 3.00-2.88(m, 1H), 2.64-2.54(m, 1H).

[0044] 13 C NMR (100MHz, CDCl 3 ): δ156.4, 132.5, 114.3, 63.6, 43.2, 36.3.

Embodiment 2

[0046] (+)-7-hydroxy-6,7-dihydro-5H-pyrrole[1,2-α]imidazole and (-)-7-hydroxy-6,7-dihydro-5H-pyrrole[1,2- Preparation of α]imidazole

[0047] CSP-HPLC method: (+)-7-hydroxyl-6,7-dihydro-5H-pyrrole[1,2-α]imidazole and (-)-7-hydroxyl- 6,7-Dihydro-5H-pyrrole[1,2-α]imidazole, ee>99%, yield 95%.

[0048] Optical resolution method: Dissolve 7-hydroxy-6,7-dihydro-5H-pyrrole[1,2-α]imidazole (14.5g, 0.11mol) in 100ml methanol in a dry 250ml two-necked bottle, stir and reflux Add (+)-tartaric acid (17.5g, 0.11mol, 1.0eq) in methanol solution 100ml, and reflux for 2h. After cooling to room temperature, a pale yellow solid was precipitated (the solid was alkalized with an appropriate amount of NaOH to liberate 7-hydroxy-6,7-dihydro-5H-pyrrole[1,2-α]imidazole, the ee value was about 30%). The above-mentioned pale yellow solid was recrystallized several times with 200 ml of methanol and a small amount of water to obtain a solid that was basified with NaOH, extracted with dichloromethane,...

Embodiment 3

[0050] Preparation of (+)-7-methoxy-6,7-dihydro-5H-pyrrole[1,2-α]imidazole

[0051] Add (+)-7-hydroxy-6,7-dihydro-5H-pyrrole[1,2-α]imidazole (128.0mg, 1.0mmol) into a dry 25ml two-necked bottle, add dry 1,4-bis Oxycycline (10ml), stirred and dissolved, put NaH (56.0mg, 1.4mmol, 1.4eq) under nitrogen atmosphere, stirred at room temperature for 2h, then slowly added MeI (0.09ml, 1.4mmol, 1.4eq), refluxed for 12h . After the volatile solvent was evaporated, it was extracted with dichloromethane (15ml×3), dried over sodium sulfate, dichloromethane was evaporated under reduced pressure, and separated by column chromatography (EtOAc / MeOH=10 / 1) to obtain 55.9 mg of a yellow oily liquid, yielding The rate is 67%.

[0052] 1 H NMR (400MHz, CDCl 3 ): δ7.13(s, 1H), 6.92(d, J=1.2Hz, 1H), 4.63(dd, J=7.2Hz, 2.0Hz, 1H), 4.18-4.10(m, 1H), 3.96-3.89 (m, 1H), 3.52(s, 3H), 2.86-2.80(m, 1H), 2.60-2.46(m, 1H).

[0053] 13 C NMR (100MHz, CDCl 3 ): δ153.0, 133.3, 114.7, 73.0, 56.4, 42.8, 34....

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Abstract

The invention relates to an iminazole chiral organic micromolecule compound with a bicyclo-structure, as shown in chemical formula (I), and a synthesizing method thereof. The compound can be applied in various asymmetric reactions as a chiral catalyst, such as asymmetric acylation, asymmetric phosphorylation, asymmetric sulfonylation, asymmetric halogenate, asymmetric Micheal addition, asymmetricSteglich rearrangement reaction, asymmetric Morita-Baylis-Hillman reaction and the like. In addition, the compound also has potential bioactivities, such as anti-ulcer, anti-depression, antibiosis andenzyme inhibitory activities and the like.

Description

technical field [0001] The invention relates to a class of imidazole chiral organic small molecule compounds with a bicyclic structure and a synthesis method thereof. Background technique [0002] The rapid rise of the chiral drug industry is mainly due to the great development of asymmetric synthesis methodology research, and in turn, the chiral drug industry has promoted the research of asymmetric synthesis methodology. Asymmetric catalytic organic synthesis is one of the most effective and beneficial methods to obtain chiral compounds. In asymmetric catalytic organic synthesis reactions, the key to achieving high reactivity and high enantioselectivity lies in the structure of chiral catalysts, and chiral organic small molecule catalysts have attracted widespread attention due to their green and stable performance. Therefore, the development of chiral organic small molecule catalysts has always been a key research area of ​​concern in academia and industry. [0003] In 1...

Claims

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Application Information

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IPC IPC(8): C07D487/04C07D471/04B01J31/02C07B53/00
Inventor 张万斌谢芳张振锋
Owner SHANGHAI JIAO TONG UNIV