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Synthesis method of chiral phosphorus-contained pyrazolone compound

A synthetic method and technology of pyrazolone, which is applied in the field of catalytic synthesis of chiral pyrazolidinone aminophosphorus compounds, can solve the problem that the substrate application range is not wide, the process yield is not very high, and there is no universal adaptability and other problems, to achieve the effect of excellent selectivity, less dosage, and easy operation

Active Publication Date: 2014-07-16
SUZHOU UNIV
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AI Technical Summary

Problems solved by technology

[0005] Jon C. Antilla et al. selected chiral magnesium phosphate reagent to catalyze imine and diphenylphosphine to carry out hydrogen phosphorylation reaction to synthesize chiral aminophosphoryl Compounds, the enantioselectivity of this process is moderate to high, there is no universal adaptability, and the catalyst is complex and difficult to synthesize (see: Ingle, G. K.; Liang, Y.; Mormino, M. G.; Li, G.; Fronczek, F. R. ; Antilla, J. C., Org. Lett. 2011, 13 (8), 2054-2057.); Wang, W et al. selected chiral multifunctional thiourea catalyzed cyclic imine and dimethyl phosphite for hydrophosphorylation Reaction reaction synthesis of phosphoramidate compounds, the yield of this process is not very high and the enantioselectivity is medium to high, the substrate application range is not wide, and there is no general adaptability (see: Xie, H.; Song, A .; Zhang, X.; Chen, X.; Li, H.; Sheng, C.; Wang, W. Chem. Commun. 2013, 49 (9), 928-930)
[0006] The prior art can synthesize chiral phosphoramidites, but has the disadvantages of low yield, complex catalyst and low selectivity, so it is necessary to find a new A method for synthesizing chiral pyrazolidinone aminophosphorus compounds, which not only has high yield and excellent enantioselectivity, but also requires mild reaction conditions and simple operation

Method used

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  • Synthesis method of chiral phosphorus-contained pyrazolone compound
  • Synthesis method of chiral phosphorus-contained pyrazolone compound
  • Synthesis method of chiral phosphorus-contained pyrazolone compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034]

[0035] Add thiourea dihydroquinine (5.9 mg, 0.01 mmol), and 2a (20.2 mg, 0.1 mmol), 1a (17.4 mg, 0.1 mmol) in turn into the reaction flask, add 0.5 mL tetrahydrofuran, and react at room temperature for 4 hours , the reaction system removes the solvent, and the crude product can be obtained by simple column chromatography (eluent: ethyl acetate:dichloromethane=3:2) to obtain the target product 3aa (35.3 mg), white solid, 94% yield, mp 224-226 °C, 95% ee.

[0036] Add dihydroquinine square amide (1.5 mg, 0.0025 mmol), 2a (20.2 mg, 0.1 mmol), 1a (17.4 mg, 0.1 mmol) in turn into the reaction flask, add 0.5 mL tetrahydrofuran, and react at room temperature for 5 hours , the reaction system removes the solvent, and the crude product can be obtained by simple column chromatography (eluent: ethyl acetate:dichloromethane=3:2) to obtain the target product 3aa (20.6 mg), white solid, 55% yield, mp 224-226 °C, 67% ee.

[0037] Add dihydroquinine square amide (3.3 mg, 0.005 m...

Embodiment 2

[0041]

[0042] In the reaction vial, dihydroquinine squaramide (6.5 mg, 0.01 mmol), and 2a (20.2 mg, 0.1 mmol), 1b (19.2mg, 0.1 mmol), add 0.5mL tetrahydrofuran, react at room temperature for 30 minutes, remove the solvent from the reaction system, and the crude product is subjected to simple column chromatography (eluent is ethyl acetate:dichloromethane=3:2 ) to get the target product 3ba (37.8 mg), white solid, yield 96%, mp 208-210°C.

[0043] The product was analyzed and the results were as follows: >99% ee, measured by HPLC [Daicel Chiralcel OD-H, hexanes / i -PrOH = 70 / 30, flow rate: 1.0 mL·min –1 , λ = 254.4 nm, t (major) = 7.850, t (minor) = 10.599]; [α] D 25 = –41.28 (c 0.625, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 8.47 (s, 1H), 7.81 (dt, J = 18.2, 7.6 Hz, 3H), 7.54 – 7.39 (m, 5H), 7.29 (td, J = 7.4, 1.1 Hz, 1H), 7.25 – 7.19 (m, 2H), 7.14 (dd, J = 13.9, 6.7 Hz, 1H), 700 –6.85(m, 2H), 5.02 (d, J = 10.3 Hz, 1H), 3.51 (dd, J = 19.9, 9.0 Hz, 1H), 3...

Embodiment 3

[0045]

[0046] In the reaction vial, dihydroquinine squaramide (6.5 mg, 0.01 mmol), and 2a (20.2 mg, 0.1 mmol), 1c (19.2mg, 0.1 mmol), add 0.5mL tetrahydrofuran, react at room temperature for 30 minutes, remove the solvent from the reaction system, and the crude product is subjected to simple column chromatography (eluent is ethyl acetate:dichloromethane=3:2 ) to get the target product 3ca (37.4mg), white solid, yield 95%, mp 201-203°C.

[0047] The product is analyzed and the results are as follows: 99% ee, measured by HPLC [Daicel Chiralcel AD-H, hexanes / i -PrOH = 70 / 30, flow rate: 1.0 mL·min –1 , λ = 210.8 nm, t (major) = 7.657, t (minor) = 15.051; [α] D 25 = –28.00 (c 0.525, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 8.72 (s, 1H), 7.80 – 7.71 (m, 2H), 7.53 – 7.37 (m, 5H), 7.36 – 7.27 (m, 3H), 7.26 – 7.18 (m, 2H), 6.84 (t, J = 8.5 Hz, 2H), 4.45 (d, J = 9.4 Hz, 1H), 3.39 (dd, J = 19.7, 9.1 Hz, 1H), 3.23 – 3.07 (m, 1H), 2.02 – 1.91 (m, 1H), 1.82 – 1.67 (m, 1...

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Abstract

The invention discloses a synthesis method of a chiral phosphorus-contained pyrazolone compound. The synthesis method concretely comprises the step: with pyrazolidinone imine and diaryl phosphorus oxide or dimethyl phosphite as a reactant, synthesizing the chiral phosphorus-contained pyrazolone compound in a solvent under the analysis of multifunctional chiral squaric acid amide. The method disclosed by the invention is simple and easy to obtain raw material, mild in reaction condition, simple and convenient for after-treatment, wide in applicable substrate range, high in yield and high in enantioselectivity; in addition, the chiral phosphorus-contained pyrazolone compound synthesized by using the method can be used for synthesizing an intermediate of a drug and an insecticide.

Description

Technical field [0001] The present invention involves the synthesis of amino phosphorus compounds, and specifically involves a catalytic synthesis method for a handphellytone amino phosphate. Background technique [0002] α-aminic acid compounds have extensive biological activity such as anti-tumor, antibotics virus, plant growth regulation, weeding, sterilization, inhibitory enzyme activity, antioxidant and radiation protection, and destroying biological cell membranes, which have attracted the attention of many scientists.Handicated pyrazolone amino phosphorus compounds as α-amin phosphoric acid derivatives also have similar potential application value. ThereforeIn great interest, many synthetic methods have emerged recently. [0003] In the field of organic synthesis, the response of asymmetric small molecules catalysis can obtain a large number of new active substances to become the most effective and economic -valuable synthetic synthetic compounds due to only a small amount...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F9/6503
Inventor 王兴旺孔令配
Owner SUZHOU UNIV
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