Method for synthesizing 2,2-disubstituted indanone compound

A synthesis method and compound technology, applied in the preparation of organic compounds, chemical instruments and methods, organic chemistry, etc., can solve the problems of cumbersome synthesis methods and low stability of raw materials, and achieve the effect of high economy and high step economy

Inactive Publication Date: 2019-10-15
CHANGZHOU UNIV
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Problems solved by technology

But this kind of reaction takes o-alkynyl benzaldehyde derivative as raw material, the stability of raw material is low, and synthetic method is loaded down with trivial details

Method used

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  • Method for synthesizing 2,2-disubstituted indanone compound
  • Method for synthesizing 2,2-disubstituted indanone compound
  • Method for synthesizing 2,2-disubstituted indanone compound

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Effect test

Embodiment 1

[0027] Under nitrogen protection, N-(2-methylpropenyl)-N-phenylacetamide 1a (0.2mmol), 3-aminoindazole 2a (0.3mmol), cuprous iodide (20mol%), peroxide Tert-butanol oxide (TBHP, 70% aqueous solution, 0.4 mmol), water (0.4 mmol), acetonitrile (1.5 mL), was added to a Schlenk reaction tube and sealed. Heating to 80°C, the reaction time was 10 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3aa was obtained by column chromatography with a yield of 72%. 1 H NMR (400MHz, CDCl 3 ): δ7.58(t, J=7.3Hz, 1H), 7.45(t, J=7.9Hz, 2H), 7.30(t, J=7.4Hz, 1H), 7.14-7.22(m, 3H), 6.71 (s,2H),4.58(d,J=13.8Hz,1H),3.69(d,J=13.8Hz,1H),3.41(d,J=17.8Hz,1H),2.86,(d,J=17.8 Hz,1H),1.75(s,3H),1.14(s,3H). 13 C NMR (100MHz, CDCl 3 ): δ208.8, 171.5, 152.6, 142.6, 135.8, 134.9, 129.1, 127.8, 127.2, 126.5, 124.0, 54.2, 50.0, 37.6, 23.6, 22.7.

Embodiment 2

[0029] Under nitrogen protection, N-(2-methylpropenyl)-N-p-tolylacetamide 1b (0.2mmol), 3-aminoindazole 2a (0.3mmol), copper acetate (10mol%), peroxide Tert-butanol (TBHP, 70% in water, 0.5 mmol), water (0.6 mmol), acetonitrile (2.5 mL), was added to a Schlenk reaction tube and sealed. Heating to 80°C, the reaction time was 10 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ba was obtained by column chromatography with a yield of 81%. 1 H NMR (400MHz, CDCl 3 ): δ7.56(t, J=7.4Hz, 1H), 7.45(q, J=7.6Hz, 2H), 7.29(t, J=7.3Hz, 1H), 6.93(d, J=7.5Hz, 2H ),6.57(s,2H),4.55(d,J=13.8Hz,1H),3.65(d,J=13.8Hz,1H),3.40(d,J=17.8Hz,1H),2.84,(d, J=17.8Hz,1H),2.26(s,3H),1.72(s,3H),1.13(s,3H). 13 C NMR (100MHz, CDCl 3 ): δ208.9, 171.6, 152.6, 140.0, 137.5, 135.8, 134.8, 129.7, 127.4, 127.1, 126.5, 124.0, 54.2, 49.9, 37.6, 23.6, 22.6, 20.9.

Embodiment 3

[0031]Under nitrogen protection, N-(2-methylpropenyl)-N-m-tolylacetamide 1c (0.2mmol), 3-aminoindazole 2a (0.4mmol), copper trifluoromethanesulfonate (10mol%) ), hydrogen peroxide (30% aqueous solution, 0.5 mmol), water (0.4 mmol), and acetonitrile (1.5 mL), were added into the Schlenk reaction tube and sealed. Heating to 80°C, the reaction time was 10 hours. After the reaction, the solvent was removed under reduced pressure, and the target product 3ca was obtained by column chromatography with a yield of 63%. 1 H NMR (300MHz, CDCl 3 ):δ7.55-7.60(m,1H),7.45(d,J=6.6Hz,2H),7.29(t,J=7.4Hz,1H),6.96-7.07(m,2H),6.56(s, 1H),6.34(s,1H),4.57(d,J=13.8Hz,1H),3.66(d,J=13.8Hz,1H),3.39(d,J=17.8Hz,1H),2.84,(d ,J=17.8Hz,1H),2.07(s,3H),1.73(s,3H),1.13(s,3H). 13 C NMR (75MHz, CDCl 3 ): δ208.7, 171.4, 152.6, 142.3, 139.0, 136.0, 134.7, 128.9, 128.6, 128.5, 127.1, 126.5, 124.6, 123.8, 54.2, 49.8, 37.4, 23.6, 22.6, 21.0.

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Abstract

The invention belongs to the field of medicines, organic chemical industry and fine chemical industry and in particular discloses a method for synthesizing a 2,2-disubstituted indanone compound. The method comprises the following specific synthesis steps: taking an N-(2-methyl allyl) amide compound and a 3-aminoindazole compound as raw materials, and heating and reacting the raw materials in an acetonitrile solvent under nitrogen protection at a temperature of 50-100 DEG C for 5-15 hours in presence of a copper salt catalyst, an oxidizing agent and water, thereby obtaining the 2,2-disubstituted indanone compound. The reaction comprises processes such as denitrification, free radical addition and hydrolysis, and involves cleavage of two C-N bonds and formation of two C-C bonds. The method disclosed by the invention opens up a new way to synthesis of the indanone structure.

Description

technical field [0001] The invention belongs to the fields of medicine, organic chemical industry and fine chemical industry, and particularly relates to a copper-catalyzed denitrogenation ring-opening reaction of 3-aminoindazole compounds, which undergoes addition, cyclization and hydrolysis steps to obtain 2,2-disubstituted indene Full ketone compounds. Background technique [0002] Indanone and its indanone structure widely exist in natural products and drug molecular fragment structures. As shown in the following formula: [0003] [0004] Among them, donepezil hydrochloride (donepezil hydrochloride) is a highly effective acetylcholinease inhibitor for the treatment of Alzheimer's disease. In addition, indanone and indanone structures are also key intermediates for the synthesis of certain structures. Therefore, the research on the synthesis method of this kind of structure has important theoretical and practical significance. The traditional indanone synthesis me...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C233/31C07C233/76C07C231/12
CPCC07C233/31C07C233/76C07C2602/24
Inventor 于金涛成江孙松滕建刚
Owner CHANGZHOU UNIV
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