Chiral spiro pyrazolone compound and preparation method thereof

A technology for spiropyrazolone and compound, which is applied in the field of compound preparation and achieves the effects of convenient and easy availability of raw materials, potential biological activity and medicinal value, and high yield

Active Publication Date: 2021-04-13
BEIJING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the stereoselective construction of chiral spiropyrazolones using pyrazolones and various 1,3-dipolar cycloaddition reactions has not been reported yet.

Method used

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  • Chiral spiro pyrazolone compound and preparation method thereof
  • Chiral spiro pyrazolone compound and preparation method thereof
  • Chiral spiro pyrazolone compound and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034]

[0035] Weigh 1a (17.4mg, 0.1mmol), 2a (32.8mg, 0.125mmol) and benzoic acid (2.4mg, 0.02mmol) in 1mL of toluene, stir at 110°C for 2 hours (use TLC to detect the reaction), and wait for the reaction After completion, the crude product was subjected to column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 1-1 / 2) to obtain the target product 3aa (40.1 mg), with a yield of 92%.

[0036] Characterization and analysis of the target object: white solid, dr>20:1; 1 H NMR (400MHz, CDCl 3 ):δ7.83-7.81(m,2H),7.46-7.42(m,2H),7.33-7.24(m,9H),7.17(d,J=7.2Hz,2H),5.78(s,1H), 4.43(s,1H),3.97-3.91(m,1H),3.28-3.21(m,1H),3.11-2.91(m,2H),1.53(s,3H)ppm; 13 C NMR (100MHz, CDCl 3 ): δ173.6, 170.9, 159.5, 137.4, 135.4, 131.9, 129.1, 129.0, 128.94, 128.90, 128.2, 126.1, 125.7, 125.1, 119.3, 77.5, 72.9, 63.9, 47.9, 32.0, 17.2ppm / z:C 27 h 25 N 4 o 2 [M+H] + The theoretically calculated value is 437.1972, and the measured value is 437.1964.

Embodiment 2

[0038]

[0039] Weigh 1b (19.2mg, 0.1mmol), 2a (32.8mg, 0.125mmol) and benzoic acid (2.4mg, 0.02mmol) in 1mL of toluene, stir at 110°C for 2 hours (use TLC to detect the reaction), and wait for the reaction After completion, the crude product was subjected to column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 1-1 / 2) to obtain the target product 3ba (32.0 mg), with a yield of 71%.

[0040] Characterization and analysis of the target object: white solid, dr>20:1; 1 H NMR (400MHz, CDCl 3 ): δ7.83-7.81(m,2H),7.46-7.42(m,2H),7.33-7.22(m,6H),7.16(d,J=7.2Hz,2H),6.99(t,J=8.6 Hz,2H),5.77(s,1H),4.40(s,1H),3.96-3.89(m,1H),3.25-3.18(m,1H),3.12-3.03(m,1H),3.00-2.92( m,1H),1.53(s,3H)ppm; 13 C NMR (100MHz, CDCl 3 ): δ173.6, 170.7, 162.9(d, J=248Hz), 159.4, 137.4, 135.3, 129.0, 128.9, 128.3, 127.9(d, J=8Hz), 127.6(d, J=3Hz), 125.8, 125.0, 119.2 , 116.1 (d, J=21Hz), 77.0, 72.9, 63.8, 47.8, 31.9, 17.1ppm; HRMS (ESI) m / z: C 27 h 24 FN 4 o2 [M+H] + The theoretical calcul...

Embodiment 3

[0042]

[0043] Weigh 1c (20.4mg, 0.1mmol), 2a (32.8mg, 0.125mmol) and benzoic acid (2.4mg, 0.02mmol) and dissolve them in 1mL of toluene, stir at 110°C for 2 hours (check the reaction with TLC), and wait for the reaction After completion, the crude product was subjected to column chromatography (eluent: ethyl acetate / petroleum ether = 1 / 1-1 / 2) to obtain the target product 3ca (36.7 mg) with a yield of 79%.

[0044] Characterization and analysis of the target object: white solid, dr>20:1; 1 H NMR (400MHz, CDCl 3 ):δ7.84-7.82(m,2H),7.45-7.41(m,2H),7.31-7.15(m,7H),6.84-6.80(m,2H),6.75(s,1H),5.77(s ,1H),4.40(s,1H),3.98-3.91(m,1H),3.61(s,3H),3.28-3.21(m,1H),3.12-3.03(m,1H),2.99-2.91(m ,1H),1.55(s,3H)ppm; 13 C NMR (100MHz, CDCl 3 ): δ173.5, 170.9, 159.8, 137.5, 135.4, 133.3, 130.0, 129.0, 128.2, 125.7, 125.0, 119.2, 118.2, 114.8, 111.2, 77.4, 72.9, 63.8, 55.1, 48.0, 32.0, 17 ) m / z: C 28 h 27 N 4 o 3 [M+H] + The theoretical calculation value is 467.2078 and the measured...

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Abstract

The invention discloses a chiral spiro pyrazolone compound and a preparation method thereof, and belongs to the technical field of compound preparation. Specifically, N, N '-cyclic imine 1, 3-dipole and pyrazolone exocyclic olefin are used as reactants, an additive and a solvent are added, a heating reaction is performed to obtain a product, and the structural formula is shown in the specification. The preparation method has the advantages of small additive dosage, short reaction time, simple post-treatment, wide substrate application range, and high yield and diastereoselectivity of most synthesized target substances. The method is a brand-new method for efficiently synthesizing the chiral spiro pyrazolone compound with potential medicinal value.

Description

technical field [0001] The invention relates to a chiral spirocyclic pyrazolone compound and a preparation method thereof, belonging to the technical field of compound preparation. Background technique [0002] Chiral spirocyclic pyrazolones are a class of advantageous drug skeleton structures with unique spatial and chemical structures and biological activities such as antitumor, antibacterial, antiviral, anti-inflammatory and analgesic. At present, most of the methods in the literature use organic small molecule catalytic strategies to realize the stereoselective construction of chiral spirocyclic pyrazolone compounds with complex and diverse structures by using various cycloaddition reactions of pyrazolones. However, the stereoselective construction of chiral spirocyclic pyrazolones using pyrazolones and various 1,3-dipolar cycloaddition reactions has not been reported yet. Therefore, by selecting pyrazolones and various 1,3-dipoles as synthetic building blocks, designin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/20
CPCC07D487/20C07B2200/07
Inventor 赵洪武汤喆范晓祖吴慧慧张恒毕晓帆蔡璐羽
Owner BEIJING UNIV OF TECH
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