CN104774202B - A kind of synthetic method of 9H-pyrido [2,3-b] Benzazole compounds - Google Patents

A kind of synthetic method of 9H-pyrido [2,3-b] Benzazole compounds Download PDF

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CN104774202B
CN104774202B CN201510161062.5A CN201510161062A CN104774202B CN 104774202 B CN104774202 B CN 104774202B CN 201510161062 A CN201510161062 A CN 201510161062A CN 104774202 B CN104774202 B CN 104774202B
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pyrido
synthetic method
benzazole compounds
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CN104774202A (en
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范学森
李彬
张新迎
郭胜海
张举
沈娜娜
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Henan Normal University
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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Abstract

The invention discloses a kind of 9HPyrido [2,3b] synthetic method of Benzazole compounds, belong to technical field of organic synthesis.Technical scheme main points are: a kind of 9HPyrido [2,3b] synthetic method of Benzazole compounds, 1 bromine 2 (2,2 dibromo vinyl) benzene or derivatives thereof, ammonia and α, β unsaturated aldehyde compounds are dissolved in organic solvent, it is subsequently adding catalyst transition metal salt and additive, prepares 9 in 60 100 DEG C of reactions in the presence of the airHPyrido [2,3b] Benzazole compounds.Building-up process of the present invention is one pot of multicomponent cascade reaction, easy and simple to handle, it is to avoid due to the use of plurality of reagents and the wasting of resources causing the purification process etc. of each step reaction intermediate and environmental pollution in multistep reaction, be 9HPyrido [2,3b] synthesis of Benzazole compounds provides a kind of economical and practical and new method of environmental protection.

Description

A kind of synthetic method of 9H-pyrido [2,3-b] Benzazole compounds
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to a kind of 9H-pyrido [2,3-b] Benzazole compounds Synthetic method.
Background technology
Indole and derivant thereof are widely present in nature, and have physiology and the biological activity of wide spectrum, and for many years one Directly by the extensive concern of chemist.Wherein, 9H-pyrido [2,3-b] indole, have another name called α-carboline, be a kind of very important Indole derivatives, is also the important feature of the natural products such as dendrodoine A, grossularines, cryptotackiene Unit.It addition, the carboline derivative of many natural origins and synthetic all has significant antiviral and active anticancer, have Important researching value.At present, the synthetic method of this compounds mainly includes the cyclisation of 2-amino indole and indole and pyridine Cyclization splicing etc..Owing to these literature methods need multistep synthesis and isolated and purified process mostly, and product yield is relatively low, the end Thing is expensive, so that its application in actual production is restricted.In view of this, exploitation pyridine synthesis diindyl it is badly in need of The new method simple and direct, efficient, green of compounds.
Summary of the invention
Present invention solves the technical problem that the synthesis side that there is provided a kind of 9H-pyrido [2,3-b] Benzazole compounds Method, this synthetic method, from the raw material of simple easily preparation, by one pot of multicomponent cascade reaction, directly obtains 9H-pyrido [2,3-b] Benzazole compounds, i.e. constructs out indole ring and pyridine ring in one pot reaction simultaneously, easy to operate, mild condition, Wide application range of substrates, is suitable for industrialized production.
The present invention solves that above-mentioned technical problem adopts the following technical scheme that, a kind of 9H-pyrido [2,3-b] indoles The synthetic method of compound, it is characterised in that: by bromo-for 1-2-(2,2-dibromo vinyl) benzene or derivatives thereof, ammonia and α, β-no Saturated aldehyde compounds is dissolved in organic solvent, is subsequently adding catalyst transition metal salt and additive, in the presence of the air in 60-100 DEG C of reaction prepares 9H-pyrido [2,3-b] Benzazole compounds, and the reaction equation in this synthetic method is:
,
Wherein R1For hydrogen, fluorine, chlorine, trifluoromethyl, methyl or methoxy, R2For hydrogen or alkyl, R3For alkyl, 1-naphthyl, 2- Thienyl, phenyl or substituted-phenyl, the substituent group on this substituted-phenyl phenyl ring is fluorine, chlorine, bromine, methyl, trifluoromethyl or methoxy One or more in base, the position of substituent group is the ortho position on phenyl ring, meta or para position, organic solvent be dimethyl sulfoxide, DMF, methyl pyrrolidone, isopropanol or dioxane, catalyst transition metal salt is Cu-lyt., bromine Changing cuprous, Hydro-Giene (Water Science). or copper acetate, additive is 1, in 10-phenanthroline, L-PROLINE, triethylene diamine or trimethylace tonitric One or more.
Limit further, the bromo-2-(2 of described 1-, 2-dibromo vinyl) benzene or derivatives thereof, ammonia and α, β-unsaturation The ratio of the amount of the material that feeds intake of aldehyde compound is 1:7-42:1-1.5.
The present invention compared with prior art has the advantage that (1) building-up process is one pot of multicomponent cascade reaction, operation Easy, it is to avoid due to the use of plurality of reagents and the purification process etc. of each step reaction intermediate is caused in multistep reaction The wasting of resources and environmental pollution；(2) raw material is cheap and easy to get or raw material is easily prepared；(3) reaction is carried out below 100 DEG C, bar Part is gentle, easy and simple to handle；(4) substrate is applied widely.Therefore, the present invention is 9H-pyrido [2,3-b] Benzazole compounds Synthesis provide a kind of economical and practical and new method of environmental protection.
Detailed description of the invention
By the following examples the foregoing of the present invention is described in further details, but this should be interpreted as this The scope inventing above-mentioned theme is only limitted to below example, and all technology realized based on foregoing of the present invention belong to this Bright scope.
Embodiment 1
Adding 1a (0.5 mmol, 170 mg), 2a (0.75 mmol, 95 mg) in the reaction tube of 25 mL, iodate is sub- Copper (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethylace tonitric (0.5 mmol, 51 Mg) and DMF (3 mL), it is subsequently adding strong aqua ammonia (7 mmol, 0.5 mL).It is heated to 80 under air DEG C, after stirring 30 hours, add 5 mL saturated ammonium chloride solution cancellation reactions, be extracted with ethyl acetate (10 mL × 2), it Rear organic phase washed with water and saturated aqueous common salt wash successively, and anhydrous sodium sulfate is dried.Filter, be spin-dried for, cross silicagel column and separate (oil Ether/ethyl acetate=10/1) obtain white solid product 3-ethyl-2-propyl group-9H-pyridine [2,3-b] indole 3a(61 mg, 51%).The sign data of this compound are as follows:1H NMR (400 MHz, CDCl3) δ: 1.06 (t, J = 7.2 Hz, 3H), 1.35 (t, J = 7.2 Hz, 3H), 1.80-1.90 (m, 2H), 2.85 (q, J = 8.0 Hz, 2H), 2.98 (t, J = 8.0 Hz, 2H), 7.25 (t, J = 7.2 Hz, 1H), 7.44 (t, J = 7.6 Hz, 1H), 7.49 (d, J = 7.6 Hz, 1H), 8.02 (d, J = 7.2 Hz, 1H), 8.13 (s, 1H), 9.75 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 14.3, 15.8, 23.5, 25.5, 37.2, 111.0, 114.6, 119.8, 120.6, 121.3, 126.2, 128.7, 138.6, 150.4, 156.9. HRMS calcd for C16H19N2: 239.1548 [M + H], found: 239.1540。
Embodiment 2
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2a (0.75 in the reaction tube of 25 mL Mmol, 95 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL). It is heated to 100 DEG C under air, after stirring 30 hours, obtains product 3-ethyl-2-propyl group-9H-pyridine [2,3-b] indole 3a(48 Mg, 40%).
Embodiment 3
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2a (0.75 in the reaction tube of 25 mL Mmol, 95 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and dimethyl sulfoxide (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL).At air Under be heated to 80 DEG C, after stirring 30 hours, obtain product 3-ethyl-2-propyl group-9H-pyridine [2,3-b] indole 3a(51 mg, 43%).
Embodiment 4
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2a (0.75 in the reaction tube of 25 mL Mmol, 95 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and isopropanol (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL).Add under air Heat is to 80 DEG C, after stirring 30 hours, obtains product 3-ethyl-2-propyl group-9H-pyridine [2,3-b] indole 3a(32 mg, and 27%).
Embodiment 5
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2a (0.75 in the reaction tube of 25 mL Mmol, 95 mg), Cu-lyt. (0.05 mmol, 4.9 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL). It is heated to 60 DEG C under air, after stirring 30 hours, obtains product 3-ethyl-2-propyl group-9H-pyridine [2,3-b] indole 3a(40 Mg, 33%).
Embodiment 6
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2a (0.75 in the reaction tube of 25 mL Mmol, 95 mg), cuprous bromide (0.05 mmol, 7.2 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL). It is heated to 80 DEG C under air, after stirring 30 hours, obtains product 3-ethyl-2-propyl group-9H-pyridine [2,3-b] indole 3a(42 Mg, 35%).
Embodiment 7
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2a (0.75 in the reaction tube of 25 mL Mmol, 95 mg), copper acetate (0.05 mmol, 9.1 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl second Acid (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL).? Heated under air to 80 DEG C, after stirring 30 hours, obtains product 3-ethyl-2-propyl group-9H-pyridine [2,3-b] indole 3a(25 mg, 21%).
Embodiment 8
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2a (0.75 in the reaction tube of 25 mL Mmol, 95 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and DMF (1.5 mL), be subsequently adding strong aqua ammonia (3.5 mmol, 0.25 ML).It is heated to 80 DEG C under air, after stirring 30 hours, obtains product 3-ethyl-2-propyl group-9H-pyridine [2,3-b] indole 3a (17 mg, 14%).
Embodiment 9
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2a (0.75 in the reaction tube of 25 mL Mmol, 95 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and DMF (6 mL), be subsequently adding strong aqua ammonia (14 mmol, 1 mL). It is heated to 80 DEG C under air, after stirring 30 hours, obtains product 3-ethyl-2-propyl group-9H-pyridine [2,3-b] indole 3a(54 Mg, 45%).
Embodiment 10
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2a (0.5 in the reaction tube of 25 mL Mmol, 63 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), 1,10-phenanthroline (0.1 mmol, 18.0 mg) and N, N- Dimethylformamide (3 mL), is subsequently adding strong aqua ammonia (21 mmol, 1.5 mL).It is heated to 80 DEG C under air, stirs 30 After hour, obtain product 3-ethyl-2-propyl group-9H-pyridine [2,3-b] indole 3a(20 mg, 17%).
Embodiment 11
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2a (0.5 in the reaction tube of 25 mL Mmol, 63 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), L-PROLINE (0.1 mmol, 11.5 mg) and N, N-bis- Methylformamide (3 mL), is subsequently adding strong aqua ammonia (21 mmol, 1.5 mL).Being heated to 80 DEG C under air, stirring 30 is little Shi Hou, obtains product 3-ethyl-2-propyl group-9H-pyridine [2,3-b] indole 3a(12 mg, and 10%).
Embodiment 12
Method as described in embodiment 1, adds 1b (0.5 mmol, 179 mg), 2a (0.75 in the reaction tube of 25 mL Mmol, 95 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL). It is heated to 80 DEG C under air, after stirring 30 hours, obtains product 7-fluoro-3-ethyl-2-propyl group-9H-pyridine [2,3-b] indole 3b (70 mg, 55%) (petrol ether/ethyl acetate=10/1).The sign data of this compound are as follows:1H NMR (400 MHz, CDCl3) δ: 1.06 (t, J = 7.2 Hz, 3H), 1.34 (t, J = 7.6 Hz, 3H), 1.64-1.71 (m, 2H), 2.84 (q, J = 7.2 Hz, 2H), 2.96 (t, J = 7.6 Hz, 2H), 6.97 (t, J = 8.8 Hz, 1H), 7.17 (d, J = 9.2 Hz, 1H), 7.90-7.94 (m, 1H), 8.06 (s, 1H), 10.01 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 14.2, 15.8, 23.6, 25.5, 37.3, 97.8, 98.1, 107.7, 108.0, 114.1, 117.7, 121.5, 121.6, 128.1, 129.1, 139.2, 139.4, 148.2, 151.0, 156.6, 160.8, 163.2. HRMS calcd for C16H18FN2: 257.1454 [M + H], found: 257.1475。
Embodiment 13
Method as described in embodiment 1, adds 1c (0.5 mmol, 188 mg), 2a (0.75 in the reaction tube of 25 mL Mmol, 95 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL). It is heated to 80 DEG C under air, after stirring 30 hours, obtains product 6-chloro-3-ethyl-2-propyl group-9H-pyridine [2,3-b] indole 3c (71 mg, 52%) (petrol ether/ethyl acetate=10/1).The sign data of this compound are as follows:1H NMR (400 MHz, CDCl3) δ: 1.18 (t, J = 7.2 Hz, 3H), 1.31 (t, J = 7.2 Hz, 3H), 1.76-1.85 (m, 2H), 2.84 (q, J = 7.2 Hz, 2H), 3.15 (t, J = 8.0 Hz, 2H), 7.41-7.46 (m, 2H), 7.97 (s, 1H), 8.30 (s, 1H), 10.02 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 14.5, 16.6, 22.4, 23.0, 31.3, 112.1, 114.0, 122.28, 122.30, 125.2, 126.0, 129.5, 137.2, 145.5, 146.9, 151.5. HRMS calcd for C16H18ClN2: 273.1158 [M + H], found: 273.1166。
Embodiment 14
Method as described in embodiment 1, adds 1d (0.5 mmol, 204 mg), 2a (0.75 in the reaction tube of 25 mL Mmol, 95 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL). It is heated to 80 DEG C under air, after stirring 30 hours, obtains product 6-trifluoromethyl-3-ethyl-2-propyl group-9H-pyridine [2,3-b] Indole 3d(83 mg, 54%) (petrol ether/ethyl acetate=10/1).The sign data of this compound are as follows:1H NMR (400 MHz, CDCl3) δ: 1.05 (t, J = 7.2 Hz, 3H), 1.36 (t, J = 7.6 Hz, 3H), 1.80-1.90 (m, 2H), 2.86 (q, J = 7.6 Hz, 2H), 3.02 (t, J = 8.0 Hz, 2H), 7.57 (d, J = 8.8 Hz, 1H), 7.68 (d, J = 8.8 Hz, 1H), 8.18 (s, 1H), 8.30 (s, 1H), 10.80 (s, 1H).13C NMR (100 MHz, CDCl3) δ: 14.1, 15.6, 23.5, 25.4, 37.3, 111.0, 114.1, 118.09, 118.13, 118.17, 118.21, 120.9, 121.8, 122.1, 122.8, 112.9, 128.9, 129.6, 140.3, 151.0, 158.2. HRMS calcd for C17H18F3N2: 307.1422[M + H], found: 307.1426。
Embodiment 15
Method as described in embodiment 1, adds 1e (0.5 mmol, 185 mg), 2a (0.75 in the reaction tube of 25 mL Mmol, 95 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL). It is heated to 80 DEG C under air, after stirring 30 hours, obtains product 6-methoxyl group-3-ethyl-2-propyl group-9H-pyridine [2,3-b] Yin Diindyl 3e(68 mg, 51%) (petrol ether/ethyl acetate=10/1).The sign data of this compound are as follows:1H NMR (400 MHz, CDCl3) δ: 1.06 (t, J = 7.2 Hz, 3H), 1.34 (t, J = 7.6 Hz, 3H), 1.81-1.91 (m, 2H), 2.83 (q, J = 8.0 Hz, 2H), 2.98 (t, J = 8.0 Hz, 2H), 3.91 (s, 3H), 7.09-7.12 (m, 1H), 7.42 (d, J = 8.8 Hz, 1H), 7.49 (s, 1H), 8.20 (s, 1H), 10.06 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 14.1, 15.6, 23.3, 25.1, 35.9, 56.0, 103.7, 112.4, 116.1, 116.3, 121.0, 128.2, 130.7, 133.4, 148.4, 153.8, 154.6. HRMS calcd for C17H21N2O: 269.1654 [M + H], found: 269.1676。
Embodiment 16
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2b (0.75 in the reaction tube of 25 mL Mmol, 53 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL). It is heated to 80 DEG C under air, after stirring 30 hours, obtains product 2-methyl-9H-pyridine [2,3-b] indole 3f(40 mg, 44%) (petrol ether/ethyl acetate=10/1).The sign data of this compound are as follows:1H NMR (400 MHz, CDCl3) δ: 2.88 (s, 3H), 7.02 (d, J = 5.2 Hz, 1H), 7.30 (t, J = 7.2 Hz, 1H), 7.50 (t, J = 7.2 Hz, 1H), 7.56 (d, J = 7.6 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H), 8.38 (d, J = 8.8 Hz, 1H), 10.46 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 23.0, 111.8, 115.1, 120.8, 121.0, 127.4, 129.4, 129.6, 131.0, 138.4, 149.3, 151.7. MS: m/z 183 [MH]+。
Embodiment 17
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2c (0.75 in the reaction tube of 25 mL Mmol, 74 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL). It is heated to 80 DEG C under air, after stirring 30 hours, obtains product 3-methyl-2-ethyl-9H-pyridine [2,3-b] indole 3g(49 Mg, 47%) (petrol ether/ethyl acetate=10/1).The sign data of this compound are as follows:1H NMR (400 MHz, CDCl3) δ: 1.39 (t, J = 7.6 Hz, 3H), 2.50 (s, 3H), 3.02 (q, J = 7.2 Hz, 2H), 7.22- 7.24 (m, 1H), 7.43 (t, J = 7.6 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 8.0 Hz, 1H), 8.09 (s, 1H), 9.88 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 13.5, 19.0, 29.0, 111.0, 114.2, 119.7, 120.6, 121.2, 122.1, 126.0, 130.0, 138.6, 150.8, 158.8. HRMS calcd for C14H15N2: 211.1235 [M + H], found: 211.1240。
Embodiment 18
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2d (0.75 in the reaction tube of 25 mL Mmol, 116 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), front three Guanidine-acetic acid (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 ML).It is heated to 80 DEG C under air, after stirring 30 hours, obtains product 3-isopropyl-2-isobutyl group-9H-pyridine [2,3-b] Yin Diindyl 3h(73 mg, 55%) (petrol ether/ethyl acetate=10/1).The sign data of this compound are as follows:1H NMR (400 MHz, CDCl3) δ: 1.08 (d, J = 6.8 Hz, 6H), 1.40 (d, J = 6.8 Hz, 6H), 2.20-2.28 (m, 1H), 3.19 (d, J = 7.2 Hz, 2H), 3.41-3.48 (m, 1H), 7.28 (t, J = 7.6 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 8.46 (s, 1H), 11.00 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 22.6, 24.6, 27.1, 29.0, 37.4, 111.2, 114.8, 119.5, 121.4, 123.0, 125.8, 134.1, 139.1, 143.4, 143.8, 150.7. HRMS calcd for C18H23N2: 267.1861 [M + H], found: 267.1846。
Embodiment 19
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2e (0.75 in the reaction tube of 25 mL Mmol, 188 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), front three Guanidine-acetic acid (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 ML).It is heated to 80 DEG C under air, after stirring 30 hours, obtains product 3-benzyl-2-phenethyl-9H-pyridine [2,3-b] indole 3i(103 mg, 57%) (petrol ether/ethyl acetate=10/1).The sign data of this compound are as follows:1H NMR (400 MHz, DMSO-d6) δ: 2.86-2.90 (m, 2H), 3.02-3.06 (m, 2H), 4.11 (s, 2H), 7.11-7.28 (m, 10H), 7.37-7.39 (m, 1H), 7.44 (d, J = 7.2 Hz, 1H), 8.04 (d, J = 7.6 Hz, 1H), 8.27 (s, 1H), 11.63 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ: 35.3, 37.4, 38.4, 111.6, 113.7, 119.6, 120.9, 121.2, 125.3, 126.2, 126.4, 126.5, 128.73, 128.74, 128.87, 128.89, 130.7, 139.4, 141.5, 142.4, 151.2, 156.7. HRMS calcd for C26H23N2: 363.1861 [M + H], found: 363.1851。
Embodiment 20
Method as described in embodiment 1, adds 1a (0.5 mmol, 170 mg), 2f in the reaction tube of 25 mL (0.75 mmol, 99 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), Trimethylace tonitric (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL).It is heated to 80 DEG C under air, after stirring 30 hours, obtains product 2-phenyl-9H-pyridine [2,3-b] indole 3j(61 Mg, 50%) (petrol ether/ethyl acetate=5/1).The sign data of this compound are as follows:1H NMR (400 MHz, DMSO-d6) δ: 7.02 (t, J = 7.6 Hz, 1H), 7.09 (d, J = 5.2 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.51-7.63 (m, 5H), 7.66-7.68 (m, 2H), 8.45 (d, J = 5.2 Hz, 1H), 12.00 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ: 111.8, 112.6, 116.4, 119.6, 120.2, 122.3, 127.0, 128.9, 129.2, 129.3, 139.0, 139.5, 144.7, 146.5, 152.8. MS: m/z 245 [MH]+。
Embodiment 21
Method as described in embodiment 1, adds 1c (0.5 mmol, 188 mg), 2f (0.75 in the reaction tube of 25 mL Mmol, 99 mg), Hydro-Giene (Water Science). (0.05 mmol, 9.5 mg), triethylene diamine (0.1 mmol, 11.2 mg), trimethyl Acetic acid (0.5 mmol, 51 mg) and DMF (3 mL), be subsequently adding strong aqua ammonia (7 mmol, 0.5 mL). It is heated to 80 DEG C under air, after stirring 30 hours, obtains product 6-chloro-2-phenyl-9H-pyridine [2,3-b] indole 3k(73 mg, 53%) (petrol ether/ethyl acetate=5/1).The sign data of this compound are as follows:1H NMR (400 MHz, DMSO-d6) δ: 7.11 (d, J = 4.8 Hz, 1H), 7.42-7.43 (m, 2H), 7.53-7.66 (m, 6H), 8.49 (d, J = 5.2 Hz, 1H), 12.22 (s, 1H). 13C NMR (100 MHz, DMSO-d6) δ: 111.9, 113.5, 116.7, 121.4, 123.6, 126.8, 128.8, 129.4, 129.5, 138.0, 138.5, 145.2, 147.5, 153.1. HRMS calcd for C17H12ClN2: 279.0689 [M + H], found: 279.0694。
Embodiment above describes the ultimate principle of the present invention, principal character and advantage.The technical staff of the industry should Understanding, the present invention is not restricted to the described embodiments, and the simply explanation present invention's described in above-described embodiment and description is former Reason, under the scope without departing from the principle of the invention, the present invention also has various changes and modifications, and these changes and improvements each fall within In the scope of protection of the invention.

Claims (1)

1. the synthetic method of 9H-pyrido [2, a 3-b] Benzazole compounds, it is characterised in that: by bromo-for 1-2-(2,2-bis- Bromo vinyl) benzene or derivatives thereof, ammonia and α, beta-unsaturated aldehyde compounds is dissolved in organic solvent, is subsequently adding catalyst Transition metal salt and additive, prepare 9H-pyrido [2,3-b] indoles chemical combination in 60-100 DEG C of reaction in the presence of the air Thing, the reaction equation in this synthetic method is:
,
Wherein R1For hydrogen, fluorine, chlorine, trifluoromethyl or methoxyl group, R2For hydrogen or alkyl, R3For alkyl or phenyl, organic solvent is two Methyl sulfoxide, DMF or isopropanol, catalyst transition metal salt is Cu-lyt., cuprous bromide, iodate Asia Copper or copper acetate, additive is 1, one or more in 10-phenanthroline, L-PROLINE, triethylene diamine or trimethylace tonitric, Described 1-bromo-2-(2,2-dibromo vinyl) benzene or derivatives thereof, ammonia and the thing that feeds intake of alpha, beta-unsaturated aldehyde compounds The ratio of the amount of matter is 1:7-42:1-1.5.
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WO1999065902A1 (en) * 1998-06-13 1999-12-23 Bayer Aktiengesellschaft METHOD FOR PRODUCING 2,4-DIMETHYLCARBOLINE AND 2,4-DIMETHYLPYRIMIDO[1,2-a]INDOLE
WO2010056194A1 (en) * 2008-11-14 2010-05-20 Astrazeneca Ab 5h-pyrrolo [ 3, 4-b] pyridin derivatives and their use
CN103483339A (en) * 2013-09-16 2014-01-01 淮阴师范学院 Simple synthesis method of 9H-pyridino-[2, 3-b] indole

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999065902A1 (en) * 1998-06-13 1999-12-23 Bayer Aktiengesellschaft METHOD FOR PRODUCING 2,4-DIMETHYLCARBOLINE AND 2,4-DIMETHYLPYRIMIDO[1,2-a]INDOLE
WO2010056194A1 (en) * 2008-11-14 2010-05-20 Astrazeneca Ab 5h-pyrrolo [ 3, 4-b] pyridin derivatives and their use
CN103483339A (en) * 2013-09-16 2014-01-01 淮阴师范学院 Simple synthesis method of 9H-pyridino-[2, 3-b] indole

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