Method for preparing chiral 4,5-dihydropyrazole compounds

A technology for dihydropyrazoles and hydrazine compounds, which is applied in chemical instruments and methods, organic compounds/hydrides/coordination complex catalysts, chemical/physical processes, etc., can solve the difficulty of raw material preparation and poor substrate adaptability , harsh reaction conditions and other problems, to achieve the effect of good reactivity, mild reaction conditions and simple synthesis

Active Publication Date: 2016-07-06
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these methods usually have the disadvantages of large amount of catalyst, harsh reaction conditions, difficult preparation of raw materials, and poor substrate adaptability.

Method used

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  • Method for preparing chiral 4,5-dihydropyrazole compounds
  • Method for preparing chiral 4,5-dihydropyrazole compounds
  • Method for preparing chiral 4,5-dihydropyrazole compounds

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Cu(OAc) 2 ·H 2 The complexation of O and L-2-1 acts as a catalyst to catalyze the reaction, and the product (R)-1,5-diphenyl-4,5-dihydropyrazole I-1 is generated.

[0060] Add metal precursor Cu(OAc) to the reaction flask 2 ·H 2 O (0.015 mmol, 5 mol%) and chiral ligand L-2-1 (0.0165 mmol, 5.5 mol%) were added under nitrogen protection with 1.0 ml of anhydrous methanol, and stirred at room temperature for 1 hour. Dissolve propargyl alcohol ester Ⅳ-1 (0.3 mmol, 1 equiv), phenylhydrazine Ⅲ-1 (0.36 mmol, 1.2 equiv) and N,N-diisopropylethylamine (0.36 mmol, 1.2 equiv) in 2.0 ml of water and methanol, and then this solution was added to the above-mentioned stirred catalyst solution under the protection of nitrogen, and the reaction was stirred at room temperature for 12 hours. After the reaction was completed, the mixture was evaporated under reduced pressure and separated by a column. Compound Ⅰ-1 was obtained as a white solid in 90% yield, 93% ee.

[0061] (R)-1,5-dip...

Embodiment 2

[0066] Reaction of L-1-1 as a ligand to produce (S)-1,5-diphenyl-4,5-dihydropyrazoleⅡ-1

[0067] The ligand L-2-1 in Example 1 is replaced by the ligand L-1-1, and the rest are the same as in Example 1. The reaction gave Compound II-1 in 52% yield and 65% ee.

[0068] The structural formula of L-1-1, Ⅱ-1 is as follows:

[0069]

Embodiment 3

[0071] L-2-2 acts as a ligand to generate (R)-1,5-diphenyl-4,5-dihydropyrazole Ⅰ-1

[0072] The ligand L-2-1 in Example 1 is replaced by the ligand L-2-2, and the rest are the same as in Example 1. The reaction yielded compound I-1 in 80% yield and 84% ee.

[0073] The structural formula of L-2-2 is as follows:

[0074]

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Abstract

The invention relates to the field of organic synthesis, and relates to a method for preparing chiral 4,5-dihydropyrazole compounds. The invention relates to a method for synthesizing the chiral 4,5-dihydropyrazole compounds through a catalyzed asymmetric [2+3] cycloaddition reaction of a hydrazine compound and a propargyl compound. An adopted chiral copper catalyst is prepared through an in-situ reaction of copper salt and a chiral tridentate P,N,N-ligand in various polar and non-polar solvents. With the method, various chiral 4,5-dihydropyrazole compounds with substituent groups can be conveniently synthesized. The percent enantiomer excess is up to 96%. The method has the characteristics of simple operation, easy-to-obtain raw materials, wide substrate application range, high enantioselectively, and the like.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for preparing chiral 4,5-dihydropyrazole compounds. Background technique [0002] The dihydropyrazole structure is considered an important structural unit in pharmacy, because many compounds containing dihydropyrazole structures have significant biological activities, such as anticancer, antibacterial, antiviral, anti-inflammatory, antimalarial, Anti-TB etc. [(a) Neuhouser, M.L.Nutr.Cancer2004, 50, 1. (b) Min, L.W.CancerTreat.Rev.2009, 35, 57; (c) Hayat, F.Salahuddin, A.Umar, S. Azam, A. Eur. J. Med. Chem. 2010, 45, 4669; (d) Girisha, K. S. Kalluraya, B. Vijaya, N. Eur. J. Med. Chem. 2010, 45, 4640; (e) Liu , X.H.Ruan, B.F.Li, J.Song, B.A.Zhu, H.L.Bhadury, P.S.Zhao, J.Mini-Rev.Med.Chem. 2011, 11, 771.]. These pharmaceutically active dihydropyrazole compounds usually contain chiral carbon centers, which are chiral dihydropyrazole compounds. Therefore, it is...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D231/06C07D409/04B01J31/24
Inventor 胡向平张德旸
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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