A kind of benzo[b,e]azepine compound based on isatin skeleton and preparation method thereof

A compound, azapine technology, applied in the field of benzo[b,e]azepine compounds and their preparation, can solve the problem of inability to obtain seven-membered ring compounds

Active Publication Date: 2019-12-10
QINGDAO AGRI UNIV
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  • Abstract
  • Description
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Problems solved by technology

At present, tetrahydropyrrolidine is a common substrate for the synthesis of nitrogen heterocyclic compounds. However, the ring-shaped products obtained by using the ring-opening and ring-expanding reaction of tetrahydropyrrolidine are all six-membered rings, eight-membered rings and nine-membered rings. ring, and the seven-membered ring compound cannot be obtained

Method used

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  • A kind of benzo[b,e]azepine compound based on isatin skeleton and preparation method thereof
  • A kind of benzo[b,e]azepine compound based on isatin skeleton and preparation method thereof
  • A kind of benzo[b,e]azepine compound based on isatin skeleton and preparation method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048]

[0049] Take 0.1 mmol of 1-benzyl-4-pyrrolidinyl isatin in a reaction bottle, add 2 mL of solvent in sequence, vertically drop 0.3 mmol of p-cresol into the bottle, and finally add the catalyst. Control the temperature of the system, keep stirring, and track the reaction by pointing samples on the thin-layer chromatographic plate until the reaction of the raw materials is complete.

[0050] After the reaction is completed, a silica gel column is used for separation and purification, and the purified product is rotary evaporated to obtain the target product.

[0051] Using the above reaction formula, 19 parallel test groups were set up, using different catalysts, solvents and reaction times. The catalysts are MsOH methanesulfonate, TfOH trifluoromethanesulfonate, Tf trifluoromethanesulfonamide 2 NH, samarium trifluoromethanesulfonate Sm (OTf) 3 , scandium trifluoromethanesulfonate Sc(OTf) 3 , Iridium trifluoromethanesulfonate Y (OTf) 3 , Gadolinium trifluorometha...

Embodiment 2

[0059] Raw materials: 1-benzyl-4-pyrrolidinyl isatin, p-cresol

[0060] Product: Chemical formula: C 26 h 25 N 2 o 3

[0061] Molecular weight: 412.49

[0062] Structural formula:

[0063] Yield: 59%

[0064] 1 H NMR (500MHz, CDCl 3 )δ7.52(s,1H),7.40–7.16(m,5H),6.97–6.85(m,2H),6.72(d,J=8.0Hz,1H),6.54(d,J=7.7Hz,1H ), 5.76(d, J=7.7Hz, 1H), 5.28(s, 1H), 4.77(q, J=15.6Hz, 2H), 4.58(dd, J=10.5, 2.3Hz, 1H), 3.74(ddd ,J=12.8,7.8,3.5Hz,1H),3.46–3.31(m,1H),2.45(ddd,J=16.4,12.2,5.9Hz,1H),2.25(s,3H),2.13–2.04(m ,1H),2.04–1.90(m,2H); 13 C NMR (125MHz, CDCl 3 )δ181.43,160.84,152.20,150.95,147.20,139.31,135.57,130.15,130.07,129.48,128.80,128.29,127.83,127.53,127.39,115.91,103.65,98.72,44.11,43.88,40.30,31.02,27.17,20.71.

Embodiment 3

[0066] Raw materials: 1-(4-methylbenzyl)-4-pyrrolidinyl isatin, p-cresol

[0067] Product: Chemical formula: C 27 h 26 N 2 o 3

[0068] Molecular weight: 426.52

[0069] Structural formula:

[0070] Yield: 45%

[0071] 1 H NMR (500MHz, CDCl 3 )δ7.51(s,1H),7.15(d,J=7.5Hz,2H),7.09(d,J=7.5Hz,2H),6.93(d,J=7.9Hz,1H),6.89(s, 1H), 6.70(d, J=8.0Hz, 1H), 6.54(d, J=7.6Hz, 1H), 5.78(d, J=7.6Hz, 1H), 5.05(s, 1H), 4.81–4.66( m,2H),4.57(d,J=10.2Hz,1H),3.81–3.66(m,1H),3.47–3.33(m,1H),2.44(dd,J=19.5,8.7Hz,1H),2.29 (s,3H),2.25(s,3H),2.13–2.04(m,1H),1.97(s,2H); 13 C NMR (125MHz, CDCl 3 )δ181.59,160.80,152.16,150.90,147.30,139.30,137.60,132.54,130.19,130.13,129.48,128.30,127.57,127.24,115.86,103.65,98.79,44.12,43.64,40.31,30.98,27.15,21.12,20.74.

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Abstract

The present invention provides a benzo[b,e]azepine compound based on an isatin skeleton, and the unique skeleton structure of the benzo[b,e]azepine compound has good antibacterial activity. A preparation method of benzo[b,e]azepine by a Lewis acid-catalyzed pyrrolidine ring-expansion synthesis process is also developed. The synthesis of polycyclic amines with complex structures is carried out by one-step method by use of 4-pyrrolidine isatin and various phenol compounds as substrates, and synthesis strategies of the polycyclic amines from pyrrolidine are extended. The synthetic method of the benzo[b,e]azepine compound has the advantages of convenient and easy-to-obtain substrate, convenient operation, high reaction activity, complete conversion of raw materials, and green economy.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and relates to a benzo[b,e]azepine compound based on an isatin skeleton and a preparation method thereof. Background technique [0002] The seven-membered nitrogen heterocyclic ring is a special class of compounds, mainly composed of heterocyclic compounds; the special structure of the seven-membered ring has significant physiological and pharmacological effects, and the potential pharmacological properties of these compounds are mainly explored in the Anticancer and antibacterial aspects. For example, Tolvaptan, a competitive antidiuretic hormone receptor blocker, and Mirtazapine, one of the eight major antidepressants. [0003] At present, the reaction strategies for the synthesis of seven-membered azacyclic 1-benzazepines include Pictet-Spengler reaction, NHC / Pd catalyzed cyclization, Ichikawa rearrangement and ring closure reaction, etc. In 1895, the "tertiary amine effect" was ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D487/04A01P1/00A01P3/00A61P31/04A61P31/10
CPCA61P31/04A61P31/10C07D487/04
Inventor 肖建王帅李帅帅于丽萍
Owner QINGDAO AGRI UNIV
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