Synthetic method of pyrrole fused-ring 3-indolone type compounds

Abstract

The invention discloses a synthetic method of pyrrole fused-ring 3-indolone type compounds. The synthetic method comprises the following step: reacting fused-ring isatin type compounds and double-substituted acetylene type compounds as raw materials in a reaction solvent under the atmosphere of nitrogen and under the action of a palladium metal catalysis and oxidation agent to obtain the pyrrole fused-ring 3-indolone type compounds. According to the synthetic method of the pyrrole fused-ring 3-indolone type compounds, disclosed by the invention, the raw materials are simple and easy to be obtained, the economy of atoms is high, the path of synthesis method is simple and convenient, and the efficiency is excellent.

Description

technical field

[0001] The invention specifically relates to a method for synthesizing pyrrole-condensed ring 3-indolinone compounds, which belongs to the technical field of organic compound technology application. Background technique

[0002] In recent years, chemists have been looking for greener organic synthesis methods. C-H bond activation has attracted the attention of many chemists due to its excellent characteristics in environmental friendliness and sustainability. Among them, through multi-site activation, one-time It is the common goal of chemists to construct a complex molecular skeleton. The present invention realizes Pd-catalyzed C-H / N-H bond breakage and completes the oxidative ring addition of alkyne compounds to construct nitrogen-containing heterocyclic compounds. This method is atom-economical High performance and short steps.

[0003] Pyrrole indole ring skeletons are widely found in a series of natural products and are an indispensable type of molecula...

Examples

Embodiment 1

[0026]

[0027] Under the protection of an inert gas, the fused ring isatin compound 1 (0.20mmol) and the alkyne compound 2a (1.00mmol) were dissolved in acetonitrile / 1,4-dioxane (2.00mL) (v / v=1:1 ), add palladium acetate (0.02mmol), silver acetate (0.40mmol), the reaction system was stirred for 12 hours at 100°C, and detected by TLC. After drying, the solvent was removed by spinning to obtain a crude product, and the product 3a was obtained by flash column chromatography with a yield of 63% (recovered yield 85%). 1 H NMR (500MHz, CDCl 3 ): δ=7.76(t, J=8.0Hz, 2H), 7.63(d, J=8.0Hz, 1H), 7.56-7.54(m, 2H), 7.46(t, J=8.5Hz, 1H), 7.38 -7.30(m, 8H), 7.20-7.17(m, 3H), 7.02(dd, J=7.0, 2.0Hz, 2H), 6.81-6.77(t, J=8.0Hz,, 1H), 6.67(d, J = 8.5Hz, 1H); 13 C NMR (125MHz, CDCl 3 ):δ=179.85,144.00,138.77,136.91,134.11,132.69,132.23,131.73,131.56,131.28,130.24,129.92,129.72,129.49,129.29,128.76,128.49,128.31,128.10,127.22,127.08,126.20,125.58, 121.40, 120.06; calculated HRMS (ESI) C 3...

Embodiment 2

[0029]

[0030] The operation steps are the same as in Example 1, and the yield is 62% (the recovered yield is 91%). 1 H NMR (500MHz, CDCl 3 ): δ=7.76-7.72(m, 2H), 7.62(d, J=8.5Hz, 1H), 7.54(dd, J=7.0, 2.0Hz, 2H), 7.26(d, J=1.5Hz, 1H) , 7.25(d, J=1.5Hz, 2H), 6.93(d d, J=7.0, 2.0Hz, 2H), 6.89(t, J=2.0Hz, 2H), 6.84(dd, J=7.0, 2.5Hz, 2H), 6.77(d, J=8.5Hz, 1H), 6.76-6.74(m, 1H), 3.85(s, 3H), 3.81(s, 3H), 3.78(s, 3H); 13 C NMR (125MHz, CDCl 3 ):δ=179.59,160.77,160.07,158.79,143.87,138.71,137.21,133.01,132.63,132.42,131.70,129.38,129.28,129.02,127.96,126.76,126.72,126.13,125.75,125.07,124.34,121.47,120.11, 114.97, 114.06, 113.77, 55.88, 55.67, 55.59; HRMS (ESI) calculated value C 36 h 27 NNaO 4 [M+Na] + 560.1832, actual value 560.1837..

Embodiment 3

[0032]

[0033] The operation steps are the same as in Example 1, and the productive rate is 52% (the productive rate is 79% after raw material recovery). 1 H NMR (500MHz, CDCl 3 ): δ=7.78(d, J=8.5Hz, 1H), 7.73(d, J=8.0Hz, 1H), 7.67(d, J=8.0Hz, 1H), 7.45-7.42(m, 2H), 7.39 -7.36(m, 3H), 7.30-7.26(m, 4H), 7.22-7.20(m, 2H), 6.93-6.89(m, 3H), 6.72(d, J=8.5Hz, 1H); 13 C NMR (125MHz, CDCl 3 ):δ=179.78,143.82,138.92,136.33,135.39,134.87,133.70,132.98,132.44,132.11,131.47,130.73,130.59,130.01,129.64,129.57,129.19,128.82,128.66,128.61,128.47,127.57,126.47, 125.20, 121.25, 120.15; HRMS (ESI) calculated value C 33 h 19 Cl 3 NNaO[M+Na] + 572.0346, actual value 572.0353..

technical field

[0001] The invention specifically relates to a method for synthesizing pyrrole-condensed ring 3-indolinone compounds, which belongs to the technical field of organic compound technology application. Background technique

[0002] In recent years, chemists have been looking for greener organic synthesis methods. C-H bond activation has attracted the attention of many chemists due to its excellent characteristics in environmental friendliness and sustainability. Among them, through multi-site activation, one-time It is the common goal of chemists to construct a complex molecular skeleton. The present invention realizes Pd-catalyzed C-H / N-H bond breakage and completes the oxidative ring addition of alkyne compounds to construct nitrogen-containing heterocyclic compounds. This method is atom-economical High performance and short steps.

[0003] Pyrrole indole ring skeletons are widely found in a series of natural products and are an indispensable type of molecula...

Examples

Embodiment 1

[0026]

[0027] Under the protection of an inert gas, the fused ring isatin compound 1 (0.20mmol) and the alkyne compound 2a (1.00mmol) were dissolved in acetonitrile / 1,4-dioxane (2.00mL) (v / v=1:1 ), add palladium acetate (0.02mmol), silver acetate (0.40mmol), the reaction system was stirred for 12 hours at 100°C, and detected by TLC. After drying, the solvent was removed by spinning to obtain a crude product, and the product 3a was obtained by flash column chromatography with a yield of 63% (recovered yield 85%). 1 H NMR (500MHz, CDCl 3 ): δ=7.76(t, J=8.0Hz, 2H), 7.63(d, J=8.0Hz, 1H), 7.56-7.54(m, 2H), 7.46(t, J=8.5Hz, 1H), 7.38 -7.30(m, 8H), 7.20-7.17(m, 3H), 7.02(dd, J=7.0, 2.0Hz, 2H), 6.81-6.77(t, J=8.0Hz,, 1H), 6.67(d, J = 8.5Hz, 1H); 13 C NMR (125MHz, CDCl 3 ):δ=179.85,144.00,138.77,136.91,134.11,132.69,132.23,131.73,131.56,131.28,130.24,129.92,129.72,129.49,129.29,128.76,128.49,128.31,128.10,127.22,127.08,126.20,125.58, 121.40, 120.06; calculated HRMS (ESI) C 3...

Embodiment 2

[0029]

[0030] The operation steps are the same as in Example 1, and the yield is 62% (the recovered yield is 91%). 1 H NMR (500MHz, CDCl 3 ): δ=7.76-7.72(m, 2H), 7.62(d, J=8.5Hz, 1H), 7.54(dd, J=7.0, 2.0Hz, 2H), 7.26(d, J=1.5Hz, 1H) , 7.25(d, J=1.5Hz, 2H), 6.93(d d, J=7.0, 2.0Hz, 2H), 6.89(t, J=2.0Hz, 2H), 6.84(dd, J=7.0, 2.5Hz, 2H), 6.77(d, J=8.5Hz, 1H), 6.76-6.74(m, 1H), 3.85(s, 3H), 3.81(s, 3H), 3.78(s, 3H); 13 C NMR (125MHz, CDCl 3 ):δ=179.59,160.77,160.07,158.79,143.87,138.71,137.21,133.01,132.63,132.42,131.70,129.38,129.28,129.02,127.96,126.76,126.72,126.13,125.75,125.07,124.34,121.47,120.11, 114.97, 114.06, 113.77, 55.88, 55.67, 55.59; HRMS (ESI) calculated value C 36 h 27 NNaO 4 [M+Na] + 560.1832, actual value 560.1837..

Embodiment 3

[0032]

[0033] The operation steps are the same as in Example 1, and the productive rate is 52% (the productive rate is 79% after raw material recovery). 1 H NMR (500MHz, CDCl 3 ): δ=7.78(d, J=8.5Hz, 1H), 7.73(d, J=8.0Hz, 1H), 7.67(d, J=8.0Hz, 1H), 7.45-7.42(m, 2H), 7.39 -7.36(m, 3H), 7.30-7.26(m, 4H), 7.22-7.20(m, 2H), 6.93-6.89(m, 3H), 6.72(d, J=8.5Hz, 1H); 13 C NMR (125MHz, CDCl 3 ):δ=179.78,143.82,138.92,136.33,135.39,134.87,133.70,132.98,132.44,132.11,131.47,130.73,130.59,130.01,129.64,129.57,129.19,128.82,128.66,128.61,128.47,127.57,126.47, 125.20, 121.25, 120.15; HRMS (ESI) calculated value C 33 h 19 Cl 3 NNaO[M+Na] + 572.0346, actual value 572.0353..

Images