Method for synthesis of 1,2,3,4,5,9-substituted benzazepine compound

A technology of benzazepine and synthesis method, which is applied in the field of organic compound process application, can solve problems such as no synthesis method proposed, and achieve the effects of promoting deep-level expansion, stable properties, and less stringent storage conditions

CN102924462BInactive Publication Date: 2015-01-14EAST CHINA NORMAL UNIV +1
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Publication Date
2015-01-14
Estimated Expiration
Not applicable · inactive patent

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Abstract

The invention discloses a method for synthesis of a 1,2,3,4,5,9-substituted benzazepine compound. The method comprises that an isatin compound and a disubstituted acetylene compound as raw materials undergo a reaction in one or more reaction solvents in the presence of a palladium catalyst and an oxidant in a nitrogen protective atmosphere to produce the 1,2,3,4,5,9-substituted benzazepine compound. The method adopts the easily available raw materials and has a simple synthesis route and high atom economical efficiency.
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Description

technical field

[0001] The invention specifically relates to a method for synthesizing 1,2,3,4,5,9-substituted benzazepine 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. This method realizes the Pd-catalyzed C-H / The N-H bond is broken, and the oxidative cycloaddition to the alkyne compound is completed to construct the nitrogen-containing heterocyclic compound. This kind of method has high atom economy and short steps. At present, the construction of benzo five-membered nitrogen ring and benzo six-membered nitrogen ring has been realized in the prior art, as shown in formula (A), but the direct synthesis of benzo seven-membered nitrogen ring by Pd-catalyzed oxidative cy...

Examples

Embodiment 1

[0023]

[0024] Under the protection of inert gas, isatin compound 1a (0.2mmol) and alkyne compound 2a (1.0mmol) were dissolved in acetonitrile / 1,4-dioxane (2mL) (v / v=1:1), Add palladium acetate (0.02mmol) and silver acetate (0.4mmol), and stir the reaction system at 100°C for 12 hours, and detect it by TLC. After the reaction, cool down to room temperature, extract several times with dichloromethane, combine the organic phases, dry, and rotate The crude product was obtained by removing the solvent, and the product 3aa was obtained by flash column chromatography with a yield of 81%. 1 H NMR (300MHz, CDCl 3 ): δ=7.56(dd, J=7.3, 1.2Hz, 1H), 7.23-6.92(m, 18H), 6.79-6.75(m, 4H); 13 C NMR (75MHz, CDCl 3 ):δ=181.83,161.85,160.11,145.38,141.57,140.51,140.24,139.62,138.22,137.25,135.87,131.39,130.79,130.76,130.67,130.42,128.39,128.27,128.19,127.58,127.48,127.07,126.86, 126.27, 124.68, 121.71; HRMS (ESI) calculated value C 36 h 24 NO 2 [M+H] + 502.1802, actual value 502.1801....

Embodiment 2

[0026]

[0027] The operating steps are the same as in Example 1, and the yield is 96%. 1 H NMR (500MHz, CDCl 3 ): δ=7.37(s, 1H), 7.13-6.87(m, 17H), 6.72(m, 4H), 2.24(s, 3H); 13 C NMR (125MHz, CDCl3 ):δ=182.03,162.12,158.11,145.26,142.09,140.59,140.49,140.37,139.55,138.33,136.91,136.23,135.88,131.42,130.77, 130.70,130.53,130.41,128.34,128.24,128.14,127.55,127.44, 127.41, 127.01, 126.79, 124.93, 121.79, 21.30; HRMS (ESI) calculated value C 37 h 26 NO 2 [M+H] + 516.1958, actual value 516.1965.

Embodiment 3

[0029]

[0030] The operating steps are the same as in Example 1, and the yield is 93%. 1H NMR (500MHz, CDCl3): δ=7.42(t, J=9.9Hz, 1H), 7.13-6.90(m, 17H), 6.79-6.72(m, 4H), 2.76(hept, J=6.9Hz, 1H ), 1.14 (d, J=6.9Hz, 6H); 13C NMR (125MHz, CDCl3): δ=182.14, 162.05, 158.30, 147.15, 145.00, 140.57, 140.42, 140.39, 139.71, 138.36, 136.90, 135.90, 131. 130.79,130.75,130.63,130.43,128.25,128.21,128.11,127.53,127.43,127.40,127.00,126.79,122.29,121.69,33.84,23.91;HRMS(ESI)计算值C39H30NO2[M+H]+544.2271,实际值544.2286 ..