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Indole-spirooxazine heterocyclic compound and preparation method thereof

A compound, the technology of indole spiro, is applied in the field of indole skeleton derivatives, which can solve problems such as uncommon methods, and achieve the effects of good greenness, high chemoselectivity, and wide applicability of substrates

Active Publication Date: 2019-03-01
JIANGXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The above methods provide many alternative approaches for the synthesis of indole spiro or nitrogen-containing heterocyclic compounds. The method is indeed uncommon, and there is currently no effective method to obtain such compounds

Method used

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  • Indole-spirooxazine heterocyclic compound and preparation method thereof
  • Indole-spirooxazine heterocyclic compound and preparation method thereof
  • Indole-spirooxazine heterocyclic compound and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025]

[0026] In a 25mL Schlenk reaction tube equipped with a magnetic stir bar, add the catalyst Rh 2 (esp) 2 (0.01mmol, 0.02equiv.), N-(3-diazo-1-methylindoline-2-ylidene)-4-methylbenzenesulfonamide (1.5mmol, 3.0equiv), benzisoxazole (0.5mmol, 1.0equiv.) and dichloromethane (5mL), nitrogen protection. The reaction solution was placed in an oil bath at 60° C. for about 2 to 4 hours. TLC detected that the reaction was complete, and then the reaction solution was cooled to room temperature. During the aftertreatment, the catalyst is removed by suction filtration through a sand core funnel equipped with silica gel, and the resulting filtrate is separated by flash column chromatography to obtain pure product 4-methyl-N-(1'-methylspiro[benzo[e] [1,3]oxazine-2,3'-indoline]-2'-methylene)benzenesulfonamide. Yield: 74%. The following is the NMR experimental data of product 3a:

[0027] 1H NMR (400MHz, DMSO) δ: 8.50(s, 1H), 7.69(d, J=8.2Hz, 2H), 7.53(d, J=6.6Hz, 1H), 7.48(t,...

Embodiment 2

[0030]

[0031] In a 25mL Schlenk reaction tube equipped with a magnetic stir bar, add the catalyst Rh 2 (esp) 2 (0.01mmol, 0.02equiv.), N-(3-diazo-1-methylindoline-2-ylidene)-4-methylbenzenesulfonamide (1.5mmol, 3.0equiv.), 5-methyl phenylisoxazole (0.5mmol, 1.0equiv.) and dichloromethane (5mL), nitrogen protection. The reaction solution was placed in an oil bath at 60° C. for about 2 to 4 hours. TLC detected that the reaction was complete, and then the reaction solution was cooled to room temperature. During the post-treatment, the catalyst is removed by suction filtration through a sand core funnel equipped with silica gel, and the obtained filtrate is separated by flash column chromatography to obtain the pure product N-(1',6-dimethylspiro[benzo[e][1 ,3]oxazine-2,3'-indoline]-2'-methylene)-4-methylbenzenesulfonamide. Yield: 58%. The following is the NMR experimental data of product 3b:

[0032] 1 H NMR (400MHz, DMSO) δ: 8.44(s, 1H), 7.69(d, J=8.2Hz, 2H), 7.46(t, J...

Embodiment 3

[0035]

[0036] In a 25mL Schlenk reaction tube equipped with a magnetic stir bar, add the catalyst Rh 2 (esp) 2 (0.01mmol, 0.02equiv.), N-(3-diazo-1-methylindoline-2-ylidene)-4-methylbenzenesulfonamide (1.5mmol, 3.0equiv), 5-chloro Benzisoxazole (0.5mmol, 1.0equiv.) and dichloromethane (5mL), nitrogen protection. The reaction solution was placed in an oil bath at 60° C. for about 2 to 4 hours. TLC detected that the reaction was complete, and then the reaction solution was cooled to room temperature. During the aftertreatment, the catalyst is removed by suction filtration through a sand core funnel equipped with silica gel, and the gained filtrate is separated by flash column chromatography to obtain pure product N-(6-chloro-1'-methylspiro[benzo[e][ 1,3]oxazine-2,3'-indoline]-2'-methylene)-4-methylbenzenesulfonamide. Yield: 52%. The following is the NMR experimental data of product 3c:

[0037] 1 H NMR (400MHz, DMSO) δ: 8.49(s, 1H), 7.72–7.66(m, 3H), 7.53–7.47(m, 2H),...

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Abstract

The invention provides an indole-spirooxazine heterocyclic compound and a preparation method thereof. According to preparation method, an indole diazo compound and benzisoxazole are adopted as oligomers, so that the oligomers react under the catalysis of transition metal, and the indole-spirooxazine heterocyclic compound is prepared through one-step reaction efficiently. The indole-spirooxazine heterocyclic compound obtained by using the method has potential medicinal activity, product molecules contain halogen, carbon-nitrogen imide double bonds and sulfonyl groups, and various additional conversions occur easily, thereby preparing an organic compound containing an indole ring system and having a more complex structure. The indole-spirooxazine heterocyclic compound and the preparation method thereof have the advantages that the raw materials are easy to obtain, the reaction system is simple, the chemoselectivity is good, the strict anhydrous and anaerobic conditions are not needed, the operability is strong, the deka-gram-level scale is amplified easily, and the reaction productivity is not also affected obviously; the compatibility of functional groups of reaction is good, the applicability of a substrate is wide, the product is stable, the separation and purification are easy, the indole-spirooxazine heterocyclic compound is suitable for industrial amplification preparation,and the application potential is better.

Description

technical field [0001] The invention relates to derivatives of indole skeleton, in particular to indole spirooxazine heterocyclic compounds and a preparation method thereof. Background technique [0002] Indole spirocyclic compounds exist in natural products and biologically active drug molecules. This type of nitrogen-containing heterocyclic skeleton has significant biological activity in drug research due to its spirocyclic quaternary carbon center: (a) Lin , H.; Danishefsky, S.J.Angew.Chem., Int.Ed.2003, 42, 36. (b) Ding, K.; Lu, Y.; .; Gao, W.; Stuckey, J.; Krajewski, K.; Roller, P.P.; c) C.V.Galliford, K.A.Scheidt, Angew.Chem.Int.Ed., 2007, 46, 8748. (d) Y.C.Lee, S.Patil, C.Golz, C.Strohmann, S.Ziegler, K.Kumar and H .Waldmann, Nat.Commun., 2017, 8, 14043.(e) Shangary, S.; Qin, D.; McEachern, D.; Liu, M.; Miller, R.S.; Qiu, S.; Nikolovska-Coleska, Z.; Ding, K.; Wang, G.; Chen, J.; Bernard, D.; Zhang, J.; ; Kang, S.; Guo, M.; Sun, Y.; Yang, D.; Wang, S.Proc.Natl.Acad...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D498/10
CPCC07D498/10C07B2200/13C07B2200/07Y02A50/30
Inventor 陈知远韩翠芬袁建军
Owner JIANGXI NORMAL UNIV
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