Beta-trifluoromethyl vinyl sulfone compounds as well as preparation method and application thereof

A technology of trifluoromethyl alkenyl sulfone and trifluoromethyl, which is applied in the application field of β-trifluoromethyl alkenyl sulfone and its preparation, anti-tumor cell proliferation, and can solve the reaction configuration selection difficult to control, harsh reaction conditions, narrow substrate range, etc., to achieve good application prospects, mild reaction conditions, and easy operation.

CN107473995AActive Publication Date: 2017-12-15FUDAN UNIV
1 Cites 8 Cited by

Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Publication Date
2017-12-15

Smart Images

  • Figure 1
    Figure 1
  • Figure 2
    Figure 2
  • Figure 3
    Figure 3
Patent Text Reader

Abstract

The invention belongs to the technical field of organic compounds and particularly provides beta-trifluoromethyl vinyl sulfone compounds, a preparation method thereof and an application of the compounds to tumor cell proliferation resistance. The beta-trifluoromethyl vinyl sulfone compounds are prepared from a multicomponent reagent (trifluoromethyl) trimethylsilane (TMSCF3), alkyne, diazonium salt and DABCO.(SO2)2 in an organic solvent DMSO through a one-step reaction. Reaction conditions are quite mild, alkyne bi-functionalization is realized directly through the one-step cascade reaction of the four raw materials, the operation is simple, defects of tedious steps, low operability and yield and poor selectivity of the traditional synthesis method of vinyl sulfone derivatives are overcome, and the method is applicable to large-scale preparation and has quite good application prospect. In-vitro pharmacological activity screening tests show that the compounds have an anti-proliferation effect on tumor cells, part of the compounds have an obvious tumor inhibition activity, the half maximal inhibitory concentration IC50 value can reach mu m level, and the compounds can be used for preparing a kind of novel anti-tumor reagents.
Need to check novelty before this filing date? Find Prior Art

Description

technical field

[0001] The invention belongs to the technical field of organic compounds, and in particular relates to novel beta-trifluoromethyl alkenyl sulfone compounds and their preparation methods, as well as their application in anti-tumor cell proliferation. Background technique

[0002] In recent years, the preparation of structurally diverse olefin derivatives through the 1,2-difunctionalization reaction of alkynes is one of the research hotspots in organic chemistry. Alkenyl sulfone compounds due to sulfonyl or sulfone group (-SO 2 The electron-pulling effect of -) and the polarity of the C-S bond activate the carbon-carbon double bond, so that alkenyl sulfone molecules can be widely used in organic synthesis as a good Michael electron acceptor. On the other hand, sulfonyl or sulfone moieties are also important pharmacophores in many bioactive molecules, the most common being sulfonamide, sulfonate and sulfone compounds widely used in clinical medicine, pesticide ...

Examples

Embodiment 1

[0026]

[0027] Add DABCO.(SO 2 ) 2 (0.16mmol), p-chlorophenylacetylene (0.2mmol), TMSCF 3 (0.24mmol), p-chlorophenyldiazotetrafluoroborate (0.24mmol) and dimethyl sulfoxide (2mL), under the protection of argon, stirred at room temperature for 8 hours, TLC detected that the reaction was complete, and the reaction solution was used Extracted with ethyl acetate, washed with saturated brine, concentrated and purified by column chromatography to obtain compound Ia.

[0028] Characterization of Compound Ia: 1 H NMR (400MHz, CDCl 3 )δ7.53–7.45(m,4H),7.33–7.28(m,2H),7.23–7.13(m,1H),7.05–6.89(m,2H); 19 F NMR (376MHz, CDCl 3 )δ-58.3(d, J=6.8Hz); 13 C NMR (100MHz, CDCl 3 )δ151.8, 141.5, 136.8, 134.6, 130.9, 130.5, 129.6, 128.6, 126.2 (q, J = 36.2Hz), 126.0, 121.3 (q, J = 274.1Hz); HRMS (ESI) calcd for C 15 h 10 Cl 2 f 3 o 2 S:380.9725(M+H + ), found: 380.9708..

Embodiment 2

[0030]

[0031] Add DABCO.(SO 2 ) 2 (0.16mmol), 3-ethynylpyridine (0.2mmol), TMSCF 3(0.24mmol), phenyldiazonium tetrafluoroborate (0.24mmol) and dimethyl sulfoxide (2mL), under the protection of argon, stirred at room temperature for 8 hours, TLC detected that the reaction was complete, and the reaction solution was washed with ethyl acetate The ester was extracted, washed with saturated brine, concentrated and purified by column chromatography to obtain compound Ib.

[0032] Characterization of compound Ib: 1 H NMR (400MHz, CDCl 3 )δ8.47(s,1H),7.74(s,1H),7.65–7.60(m,3H),7.47–7.43(m,3H),7.30(d,J=6.0Hz,1H),7.26–7.16 (m,1H); 19 F NMR (376MHz, CDCl 3 )δ-59.2(d, J=5.5Hz).; 13 C NMR (100MHz, CDCl 3 )δ151.5, 149.4, 141.5, 136.4, 134.4, 132.7, 129.2, 129.1, 126.4 (q, J = 36.7Hz), 125.5, 124.3, 121.3 (q, J = 273.8Hz); HRMS (ESI) calcdfor C 14 h 11 f 3 NO 2 S:314.0457(M+H + ), found: 314.0463..

Embodiment 3

[0034]

[0035] Add DABCO.(SO 2 ) 2 (0.16mmol), p-acetylphenylacetylene (0.2mmol), TMSCF 3 (0.24mmol), phenyldiazonium tetrafluoroborate (0.24mmol) and dimethyl sulfoxide (2mL), under the protection of argon, stirred at room temperature for 8 hours, TLC detected that the reaction was complete, and the reaction solution was washed with ethyl acetate The ester was extracted, washed with saturated brine, concentrated and purified by column chromatography to obtain compound Ic.

[0036] Characterization of Compound Ic: 1 H NMR (400MHz, CDCl 3 )δ7.85(d, J=8.5Hz, 2H), 7.63(t, J=7.3Hz, 1H), 7.58–7.55(m, 2H), 7.45(t, J=7.8Hz, 2H), 7.19( q, J=7.1Hz, 1H), 7.10(d, J=8.3Hz, 2H), 2.59(s, 3H); 19 F NMR (376MHz, CDCl 3 )δ-58.3(d, J=7.2Hz); 13 C NMR (100MHz, CDCl 3 )δ197.2, 152.3, 137.9, 135.9, 134.6, 132.5, 129.9, 129.3, 129.1, 127.8, 125.8 (q, J = 36.1Hz), 121.3 (q, J = 273.5Hz), 26.6; HRMS (ESI) calcd for C 17 h 14 f 3 o 3 S:355.0610(M+H + ), found: 355.0617..