CN103232462B - The synthetic method of coumarin-pyrrole compound - Google Patents

The synthetic method of coumarin-pyrrole compound Download PDF

Info

Publication number
CN103232462B
CN103232462B CN201310174499.3A CN201310174499A CN103232462B CN 103232462 B CN103232462 B CN 103232462B CN 201310174499 A CN201310174499 A CN 201310174499A CN 103232462 B CN103232462 B CN 103232462B
Authority
CN
China
Prior art keywords
dmso
coumarin
synthetic method
pyrrole compound
cnmr
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN201310174499.3A
Other languages
Chinese (zh)
Other versions
CN103232462A (en
Inventor
彭艳红
高涛
汪舰
孙绍发
吴鸣虎
郭海滨
朱晓明
黄文平
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hubei University of Science and Technology
Original Assignee
Hubei University of Science and Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hubei University of Science and Technology filed Critical Hubei University of Science and Technology
Priority to CN201310174499.3A priority Critical patent/CN103232462B/en
Publication of CN103232462A publication Critical patent/CN103232462A/en
Application granted granted Critical
Publication of CN103232462B publication Critical patent/CN103232462B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Landscapes

  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention discloses a kind of synthetic method of coumarin-pyrrole compound, in reaction solvent, with 4-aminocoumarin compounds and two replaced acetylene compounds for raw material, under palladium (II) catalysis, oxygenant effect, be obtained by reacting coumarin-pyrrole compound.Cheaper starting materials of the present invention is easy to get, and reaction conditions is gentle, and synthetic method route is easy, and Atom economy is high, has good prospects for commercial application.

Description

The synthetic method of coumarin-pyrrole compound
Technical field
The invention belongs to organic compound process application technical field, be specifically related to a kind of coumarin-pyrrole compound synthetic method.
Background technology
Because nitrogen heterocyclic is prevalent in natural product and medicine, be people's priority fields of studies.As everyone knows, pyrroles is Five-membered Heterocyclic Compounds, and many drug molecules comprise this type of skeleton, therefore in pharmaceutical chemistry, are used as basic structural unit, such as formula A, the trade names sold by Pfizer is the blood lipid-lowering medicine atorvastatin (Atorvastatin) of Lipitor 1, the cancer cells different to many kinds have cytotoxicity and the topoisomerase I 60 of the mankind had to the Lamellarin D (LamellarinD) of strongly inhibited effect 2, there is NSAID (non-steroidal anti-inflammatory drug) (NSAID) zomepirac (Zomepirac) of antipyretic effect 3with potential cancer therapy drug 4.
The several drug molecule containing pyrrole structure unit of formula A.
The method of many synthesis pyrroles is reported.Traditional method has Knorr, Paal-Knorr and Hantzsch reacts.Although these methods effectively can synthesize pyrrole derivative, still there is many obvious defects in the reaction of these classics, and the utilization ratio as starting raw material is low, reactions steps is many, severe reaction conditions etc., and these all limit the use range of above method.Except traditional method, transition metal-catalyzed cycloaddition reaction is mainly used in the synthesis of present pyrrole derivative, as shown in the formula B(a) shown in, the active C of aromatic ring-the orienting group (DG) on H key produces the base pyrrole derivative of different replacement with alkynes to utilize Rh (III) or Ru (III) catalyzed oxidation to be coupled.Although the introducing of orienting group achieves huge progress, need through polystep reaction, the synthesis of azole compounds is more prone to the one-step synthesis B(b avoiding using orienting group).
Present invention achieves Pd(II) catalyzed oxidation cycloaddition " lock "-auxiliary trans-enamine and alkynes one step build coumarin-pyrrole compound, synthetic method route of the present invention is easy, reaction conditions is gentle, atom economy type is high, usefulness is superior, achieve the breakthrough of this system chemosynthesis, and promote that the profound level of this system related drugs chemical research is expanded.
Formula B. utilizes active C-and H key prepares the synthetic schemes of pyrroles.A) orienting group (DG) secondary path; B) " lock " secondary path (omnidirectional substituting group).
Summary of the invention
The object of the present invention is to provide a kind of synthetic method of coumarin-pyrrole compound, in reaction solvent, with 4-aminocoumarin compounds and two replaced acetylene compounds for raw material, under palladium (II) catalysis, oxygenant effect, be obtained by reacting coumarin-pyrrole compound.Reaction process is as shown in the formula (I):
Formula (I)
Wherein, R 1for hydrogen atom, alkyl, methoxyl group, aryl or halogen; R 2, R 3for alkyl, ester group, aryl, benzene, connect benzene or heterocycle.In the present invention, R 1, R 2, R 3include but are not limited to above-mentioned group.
In the present invention, in reaction flask, by 4-aminocoumarin compounds 1(Xmmol), two replaced acetylene compounds 2(Ymmol), metallic palladium (Ummol) and oxygenant (Vmmol) be dissolved in DMSO(ZmL) in, at r.t., W hour is reacted under oxygen ambient conditions, TLC detects, and after completion of the reaction, rapid column chromatography obtains product 3(coumarin-pyrrole compound).
In the synthetic method of coumarin-pyrrole compound of the present invention, described metallic palladium is Pd (OAc) 2.
Wherein, described metallic palladium consumption is 0.1 equivalent of 4-aminocoumarin compounds.
Wherein, described oxygenant is AgOAc, CuCl 2, Cu (OAc) 2, Isosorbide-5-Nitrae-benzoquinones, DDQ, oxygen or ozone.
Wherein, described oxygenant consumption is 0.2 equivalent for 4-aminocoumarin compounds.
Wherein, described reaction solvent is any one or arbitrary combination of N,N-dimethylacetamide, methyl-2-pyrrolidone, acetonitrile, methyl-sulphoxide.
Wherein, described 4-aminocoumarin compounds concentration is 0.1mmol/L, and described pair of replaced acetylene compounds concentration is 0.3mmol/L.
Wherein, described pair of replaced acetylene compounds equivalents is 3 equivalents.
Wherein, described reaction is 25-120 ocarry out at C temperature.
Advantage of the present invention comprises: each raw material used in synthetic method of the present invention is simple and easy to get, is industrialization commodity, wide material sources, cheap, and stable in properties, preservation condition is not harsh; Secondly, this synthetic method is simple, processing ease, product yield are high, and practicality is especially remarkable; In addition, the present invention has that cost is low, efficiency is high, technique is simple, pollute few characteristic, achieves the breakthrough of this system chemosynthesis, and promotes that the profound level of this system related drugs chemical research is expanded.
The coumarin-pyrrole compound that the present invention builds has good biological activity, for the core skeleton of high amount of drug bioactive molecule, as: blood lipid-lowering medicine atorvastatin (Atorvastatin) has Cytotoxic Lamellarin D (LamellarinD) etc. with the cancer cells different to many kinds, meanwhile, this structure is also the very important a kind of structural design elements of medicinal chemistry art.This compounds biological activity is good, and using value is higher, and the present invention is medicament research and development, the high flux screening of small-molecule drug and the complete synthesis of complicated natural product provide practicality, efficiently novel method.
Embodiment
In conjunction with following specific embodiment, the present invention is described in further detail, and protection content of the present invention is not limited to following examples.Under the spirit and scope not deviating from inventive concept, the change that those skilled in the art can expect and advantage are all included in the present invention, and are protection domain with appending claims.Implement process of the present invention, condition, reagent, experimental technique etc., except the following content mentioned specially, be universal knowledege and the common practise of this area, the present invention is not particularly limited content.Data given by following examples comprise concrete operations and reaction conditions and product.Product purity is identified by nuclear-magnetism.
Embodiment 1
By coumarin kind compound 1a(0.2mmol), two replaced acetylene compounds 2a(0.6mmol), palladium (0.02mmol) and neutralized verdigris (0.04mmol) join in DMSO (2mL).This reaction mixture, at normal temperature and pressure, stirs 72 hours under oxygen atmosphere.After completion of the reaction, underpressure distillation is removed organic solvent and is obtained crude product in TLC monitoring, and rapid column chromatography (ethyl acetate: normal hexane=1:4) obtains product 3aa(90%). 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.80 (s, 1H), 8.37 – 8.17 (m, 1H), 7.56 – 7.20 (m, 13H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.74,151.61,135.78,133.88,133.55,131.49,131.07,129.24,128.82,128.18,128.09,127.14,124.39,122.11,121.09,117.00,113.86,107.29,40.73,40.46,40.18,39.90,39.62,39.35,39.07.HRMS (ESI): calculated value [C 23h 15nO 2+ H] +338.1176, actual value 338.1177.
Embodiment 2
Operation steps with embodiment 1, productive rate 89%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.72 (s, 1H), 8.11 (s, 1H), 7.65 – 7.08 (m, 12H), 2.43 (s, 3H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.87,149.80,135.82,133.73,133.61,133.49,131.48,131.06,130.09,128.80,128.70,128.13,128.10,127.14,121.91,121.06,116.77,113.52,107.32,40.73,40.46,40.18,39.90,39.62,39.35,39.07,20.99.HRMS (ESI): calculated value [C 24h 17nO 2-H] -350.1187, actual value 350.1197.
Embodiment 3
Operation steps with embodiment 1, productive rate 99%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.75 (s, 1H), 8.16 (s, 1H), 7.65 – 6.92 (m, 12H), 2.74 (q, j=7.6Hz, 2H), 1.30 (t, j=7.6Hz, 3H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 158.01,150.04,139.93,136.07,133.85,133.70,131.62,131.17,129.18,128.93,128.85,128.27,128.22,127.25,121.15,120.79,116.91,113.68,107.36,40.73,40.46,40.18,39.90,39.62,39.35,39.07,28.18,15.89.HRMS (ESI): calculated value [C 25h 19nO 2-H] -364.1343, actual value 364.1346.
Embodiment 4
Operation steps with embodiment 1, productive rate 92%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.59 (s, 1H), 8.18 (d, j=8.4Hz, 1H), 7.51 – 7.08 (m, 10H), 7.18 – 6.78 (m, 2H), 3.85 (s, 3H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 160.59,158.04,153.31,136.70,133.80,133.07,131.74,131.16,128.91,128.78,128.18,128.10,127.17,123.22,120.82,112.20,107.18,105.62,101.67,56.12,40.73,40.46,40.18,39.90,39.62,39.35,39.07.HRMS (ESI): calculated value [C 24h 17nO 3-H] -366.1136, actual value 366.1138.
Embodiment 5
Operation steps with embodiment 1, productive rate 72%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.76 (s, 1H), 8.07 (dd, j=9.2,3.0Hz, 1H), 7.45 (m, 1H), 7.40 – 7.23 (m, 11H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 159.48,157.58,148.00,135.03,135.02,134.42,133.45,131.43,131.15,129.00,128.79,128.43,128.24,127.36,121.33,119.06,118.99,116.39,116.19,114.93,114.85,107.99,107.78,107.73,40.73,40.46,40.18,39.90,39.62,39.35,39.07.HRMS (ESI): calculated value [C 23h 14fNO 2-H] -354.0936, actual value 354.0931.
Embodiment 6
Operation steps with embodiment 1, productive rate 89%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.81 (s, 1H), 8.54 (d, j=2.2Hz, 1H), 7.62 (dd, j=8.8,2.2Hz, 1H), 7.45 – 7.22 (m, 11H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.37,150.70,134.47,134.46,133.43,131.65,131.37,131.13,128.99,128.69,128.44,128.29,127.42,124.56,121.39,119.38,116.36,115.89,107.87,40.73,40.46,40.18,39.90,39.62,39.35,39.07.HRMS (ESI): calculated value [C 23h 14brNO 2-H] -414.0135, actual value 414.0141.
Embodiment 7
Operation steps with embodiment 1, productive rate 79%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.80 (s, 1H), 8.39 (d, j=2.3Hz, 1H), 7.52 – 7.42 (m, 2H), 7.40 – 7.20 (m, 10H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.39,150.27,134.56,134.45,133.44,131.37,131.13,128.98,128.83,128.70,128.48,128.43,128.27,127.40,121.60,121.39,119.04,115.38,107.85,40.73,40.46,40.18,39.90,39.62,39.35,39.07.HRMS (ESI): calculated value [C 23h 14clNO 2-H] -370.0640, actual value 370.0643.
Embodiment 8
Operation steps with embodiment 1, productive rate 95%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.69 (s, 1H), 7.84 (d, j=2.5Hz, 1H), 7.54 – 7.15 (m, 11H), 7.02 (dd, j=8.9,2.5Hz, 1H), 3.85 (s, 3H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 158.01,155.99,146.06,135.98,133.94,133.65,131.64,131.18,128.97,128.86,128.31,128.20,127.25,121.20,118.20,116.76,114.24,107.50,104.90,56.15,40.73,40.46,40.18,39.90,39.62,39.35,39.07.HRMS (ESI): calculated value [C 24h 17nO 3-H] -366.1136, actual value 366.1139.
Embodiment 9
Operation steps with embodiment 1, productive rate 97%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.83 (s, 1H), 8.26 (d, j=8.4Hz, 1H), 7.56 (s, 1H), 7.51 – 7.42 (m, 1H), 7.40 – 7.21 (m, 10H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.31,152.05,135.12,134.26,133.45,133.27,131.43,131.13,128.95,128.86,128.38,128.24,127.34,124.73,123.54,121.29,117.16,112.99,107.23,40.73,40.46,40.18,39.90,39.62,39.35,39.07.HRMS (ESI): calculated value [C 23h 14clNO 2-H] -370.0640, actual value 370.0628.
Embodiment 10
Operation steps with embodiment 1, productive rate 60%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.74 (s, 1H), 8.12 (d, j=7.5Hz, 1H), 7.60 – 6.85 (m, 12H), 2.42 (s, 3H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.30,149.55,135.82,133.48,133.21,131.13,130.67,130.06,128.48,128.43,127.78,127.72,126.75,125.39,123.51,120.57,119.43,113.13,106.76,40.73,40.46,40.18,39.90,39.62,39.35,39.07,15.75.HRMS (ESI): calculated value [C 24h 17nO 2-H] -350.1187, actual value 350.1181.
Embodiment 11
Operation steps with embodiment 1, productive rate 96%. 1hNMR (500MHz, d 6-DMSO, 373K): δ 12.66 (s, 1H), 8.05 (s, 1H), 7.65 – 6.85 (m, 11H), 2.33 (s, 6H). 13cNMR (125MHz, d 6-DMSO, 373K): δ 158.11,150.21,138.57,136.25,133.81,133.43,132.69,131.67,131.17,128.91,128.76,128.20,128.17,127.22,122.34,121.05,117.57,111.40,106.95,40.73,40.46,40.18,39.90,39.62,39.35,39.07,20.08,19.60.HRMS (ESI): calculated value [C 25h 19nO 2-H] -364.1343, actual value 364.1342.
Embodiment 12
Operation steps with embodiment 1, productive rate 98%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.79 (s, 1H), 8.36 (d, j=8.0Hz, 1H), 8.32 (d, j=8.6Hz, 1H), 7.97 (d, j=8.0Hz, 1H), 7.86 (d, j=8.6Hz, 1H), 7.65 (t, j=7.2Hz, 1H), 7.60 (t, j=7.1Hz, 1H), 7.42 – 7.23 (m, 10H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.71,147.25,136.84,134.12,133.65,133.36,131.61,131.21,128.99,128.93,128.56,128.30,128.24,127.63,127.28,124.35,123.35,121.76,121.15,119.45,109.19,107.32,40.73,40.46,40.18,39.90,39.62,39.35,39.07.HRMS (ESI): calculated value [C 27h 17nO 2-H] -386.1187, actual value 386.1177.
Embodiment 13
Operation steps with embodiment 1, productive rate 60%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 8.08 (d, j=8.0Hz, 1H), 7.60 – 7.36 (m, 6H), 7.32-7.26 (m, 2H), 7.24 – 7.11 (m, 5H), 4.25 (s, 2H), 2.16 – 1.70 (m, 1H), 0.67 (d, j=5.9Hz, 6H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.52,151.79,139.07,133.87,133.35,132.32,131.31,130.78,129.15,129.09,128.91,127.61,126.86,124.81,122.74,122.34,117.90,114.33,107.67,53.05,40.51,40.34,40.17,40.01,39.84,39.67,39.51,29.23,19.82.HRMS (EI): calculated value [C 27h 23nO 2] +393.1729, actual value 393.1727.
Embodiment 14
Operation steps with embodiment 1, productive rate 85%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 11.68 (s, 1H), 7.73 – 6.72 (m, 10H), 2.76 (s, 2H), 2.24 (s, 2H), 1.10 (s, 6H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 192.43,143.53,135.62,132.58,131.01,129.38,128.73,127.92,127.71,127.02,126.53,119.61,117.30,53.38,40.51,40.34,40.17,40.01,39.84,39.67,39.51,36.70,35.34,28.66.HRMS (ESI): calculated value [C 22h 21nO+H] +316.1696, actual value 316.1694.
Embodiment 15
Operation steps with embodiment 1, productive rate 85%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 11.73 (s, 1H), 7.21 (m, 10H), 2.87 (t, j=5.8,2H), 2.33 (t, j=6.0,2H), 2.12 – 2.03 (m, 2H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 192.97,144.74,135.77,132.56,130.99,129.17,128.73,127.92,127.71,127.04,126.52,119.78,118.53,40.51,40.34,40.17,40.01,39.84,39.67,39.51,39.29,23.82,22.98.HRMS (ESI): calculated value [C 20h 17nO+H] +288.1388, actual value 288.1388.
Embodiment 16
Operation steps with embodiment 1, productive rate 94%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.68 (s, 1H), 8.26 (d, j=7.6,1H), 7.51 – 7.45 (m, 1H), 7.44 – 7.34 (m, 2H), 7.29 – 7.23 (m, 2H), 7.22 – 7.16 (m, 4H), 7.15 – 7.10 (m, 2H), 2.32 (s, 3H), 2.30 (s, 3H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.86,151.67,137.67,136.23,135.64,133.92,131.02,130.73,129.51,129.24,128.85,128.81,128.75,124.47,122.17,120.79,117.09,114.03,107.40,40.76,40.48,40.20,39.93,39.65,39.37,39.09,21.30,21.24.HRMS (ESI): calculated value [C 25h 19nO 2-H] -364.1343, actual value 364.1348.
Embodiment 17
Operation steps with embodiment 1, productive rate 95%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.63 (s, 1H), 8.25 (d, j=7.6Hz, 1H), 7.41 (m, 3H), 7.29 (d, j=8.6Hz, 2H), 7.21 (d, j=8.5Hz, 2H), 6.94 (d, j=8.6Hz, 2H), 6.88 (d, j=8.5Hz, 2H), 3.77 (s, 3H), 3.76 (s, 3H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 159.32,158.57,157.94,151.62,135.36,133.70,132.26,130.18,129.10,125.88,124.44,124.08,122.09,120.05,117.07,114.45,114.07,113.72,107.37,55.65,55.44,40.76,40.48,40.20,39.93,39.65,39.37,39.09.HRMS (ESI): calculated value [C 25h 19nO 4-H] -396.1241, actual value 396.1249.
Embodiment 18
Operation steps with embodiment 1, productive rate 86%. 1hNMR (500MHz, d 6-DMSO, 373K): δ 12.58 (s, 1H), 8.26 (d, j=7.2Hz, 1H), 7.66 – 7.12 (m, 11H). 13cNMR (125MHz, d 6-DMSO, 373K): δ 157.69,152.07,136.33,133.36,133.09,132.86,132.59,132.40,130.63,130.43,129.46,129.00,128.27,124.37,122.28,120.61,117.11,114.02,107.76,40.76,40.48,40.20,39.93,39.65,39.37,39.09.HRMS (ESI): calculated value [C 23h 13cl 2nO 2-H] -404.0251, actual value 404.0256.
Embodiment 19
Operation steps with embodiment 1, productive rate 80%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.75 (s, 1H), 8.29 (d, j=7.4Hz, 1H), 7.81 – 7.49 (m, 9H), 7.47 – 7.33 (m, 2H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.62,152.19,137.93,136.94,135.45,133.07,131.89,129.74,129.62,129.17,128.91,128.50,128.25,125.99,125.82,125.79,125.76,125.67,125.08,125.05,125.02,124.99,124.45,123.82,123.51,122.41,121.28,117.18,113.91,107.92,40.76,40.48,40.20,39.93,39.65,39.37,39.09.HRMS (ESI): calculated value [C 25h 13f 6nO 2-H] -472.0778, actual value 472.0793.
Embodiment 20
Operation steps with embodiment 1, productive rate 84%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.82 (s, 1H), 8.16 (d, j=7.6Hz, 1H), 7.54 – 7.32 (m, 3H), 7.32 – 7.07 (m, 6H), 7.05 – 6.95 (m, 2H), 2.12 (s, 6H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.84,151.66,137.66,137.58,135.26,134.08,133.53,131.61,131.58,131.42,130.47,129.74,129.11,128.97,127.35,125.94,125.27,124.44,121.76,121.04,117.06,114.10,107.56,40.76,40.48,40.20,39.93,39.65,39.37,39.09,20.07,20.03.HRMS (ESI): calculated value [C 25h 19nO 2-H] -364.1343, actual value 364.1348.
Embodiment 21
Operation steps with embodiment 1, productive rate 90%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.74 (s, 1H), 8.29 (d, j=7.7Hz, 1H), 7.50 – 7.47 (m, 1H), 7.45 – 7.35 (m, 2H), 7.28 (s, 1H), 7.24 – 7.17 (m, 2H), 7.17 – 7.10 (m, 3H), 7.09 – 7.02 (m, 2H), 2.29 (s, 3H), 2.27 (s, 3H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.82,151.71,138.03,137.01,135.74,133.97,133.65,131.75,131.54,129.30,128.87,128.71,128.26,128.04,127.91,126.05,124.47,122.22,121.26,117.10,114.00,107.43,40.76,40.48,40.20,39.93,39.65,39.37,39.09,21.52.HRMS (ESI): calculated value [C 25h 19nO 2-H] -364.1343, actual value 364.1349.
Embodiment 22
Operation steps with embodiment 1, productive rate 93%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.65 (s, 1H), 8.29 (dd, j=7.6,1.1Hz, 1H), 7.50 – 7.44 (m, 1H), 7.44 – 7.34 (m, 2H), 6.99 (s, 2H), 6.96 – 6.93 (m, 2H), 6.91 (s, 2H), 2.23 (s, 6H), 2.20 (s, 6H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.78,151.72,137.69,136.76,135.58,133.95,133.61,131.47,129.60,129.25,128.89,128.65,126.48,124.43,122.22,121.34,117.09,114.03,107.47,40.76,40.48,40.20,39.93,39.65,39.37,39.09,21.39.HRMS (ESI): calculated value [C 27h 23nO 2-H] -392.1656, actual value 392.1669.
Embodiment 23
Operation steps with embodiment 1, productive rate 62%. 1hNMR (500MHz, d 6-DMSO, 373K): δ 12.91 (s, 1H), 8.27 (d, j=7.7Hz, 1H), 7.96 – 7.78 (m, 5H), 7.73 (m, 1H), 7.59 – 7.25 (m, 11H). 13cNMR (125MHz, d 6-DMSO, 373K): δ 157.61,152.26,135.95,134.15,133.70,133.57,133.52,132.87,132.09,129.79,129.59,129.21,128.87,128.50,128.21,127.69,126.85,126.56,126.42,126.12,125.91,125.73,125.40,125.26,124.38,122.17,121.10,117.16,114.55,108.96,40.76,40.48,40.20,39.93,39.65,39.37,39.09.HRMS (ESI): calculated value [C 31h 19nO 2-H] -436.1343, actual value 436.1356.
Embodiment 24
Operation steps with embodiment 1, productive rate 60%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.91 (s, 1H), 8.25 (d, j=7.6Hz, 1H), 7.61 (d, j=5.1Hz, 1H), 7.57 (d, j=5.1Hz, 1H), 7.53 – 7.45 (m, 2H), 7.44 – 7.35 (m, 2H), 7.21 – 7.16 (m, 1H), 7.16 – 7.07 (m, 2H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.36,151.91,136.05,133.45,132.25,129.89,129.73,128.06,127.66,127.58,127.48,124.62,122.35,117.21,113.65,113.60,108.25,40.76,40.48,40.20,39.93,39.65,39.37,39.09.HRMS (ESI): calculated value [C 19h 11nO 2s 2-H] -348.0158, actual value 348.0158.
Embodiment 25
Operation steps with embodiment 1, productive rate 63%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.07 (s, 1H), 7.99 (d, j=7.3Hz, 1H), 7.43 – 7.29 (m, 3H), 2.68 (qd, j=7.4,4.7Hz, 4H), 1.24 (t, j=7.6Hz, 3H), 1.14 (t, j=7.4Hz, 3H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 158.61,151.43,135.80,134.04,128.36,124.33,121.27,120.53,117.08,114.39,106.79,40.76,40.48,40.20,39.93,39.65,39.37,39.09,18.74,17.57,16.75,15.40.HRMS (ESI): calculated value [C 15h 15nO 2-H] -240.1030, actual value 240.1038.
Embodiment 26
Operation steps with embodiment 1, productive rate 88%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.78 (m, 1H), 8.27 (m, 1H), 7.70 – 6.90 (m, 12H), 0.26 (m, 9H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.86,157.82,151.72,151.69,139.95,138.19,135.99,135.94,134.15,134.08,133.90,133.70,133.00,132.04,131.64,131.15,130.51,129.38,129.12,128.97,128.38,128.25,128.06,127.30,124.51,122.23,122.20,121.36,121.04,117.11,113.93,107.51,107.26,40.76,40.48,40.20,39.93,39.65,39.37,39.09 ,-0.56 ,-0.74.HRMS (ESI): calculated value [C 26h 23nO 2si-H] -408.1425, actual value 408.1428.
Embodiment 27
Operation steps with embodiment 1, productive rate 92%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.72 (s, 1H), 8.35 – 8.13 (m, 1H), 7.57 – 7.09 (m, 10H), 7.02 – 6.80 (m, 2H), 3.77 (m, 3H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 159.39,158.66,157.92,157.88,151.70,151.63,135.74,135.53,134.04,133.83,133.66,132.25,131.76,131.19,130.26,129.30,129.20,128.96,128.86,128.19,127.14,125.66,124.50,123.88,122.19,122.13,120.96,120.28,117.11,114.44,114.02,113.74,107.44,107.30,55.65,55.45,40.76,40.48,40.20,39.93,39.65,39.37,39.09.HRMS (ESI): calculated value [C 24h 17nO 3-H] -366.1136, actual value 366.1144.
Embodiment 28
Operation steps with embodiment 1, productive rate 81%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.82 (s, 1H), 8.25 (m, 1H), 7.60 – 7.08 (m, 12H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 163.10, 162.74, 161.15, 160.80, 157.92, 157.82, 151.71, 135.90, 135.89, 134.12, 133.47, 133.11, 133.05, 133.03, 131.42, 131.15, 131.10, 131.04, 129.94, 129.92, 129.43, 129.04, 128.96, 128.41, 128.29, 128.09, 128.06, 127.33, 124.57, 124.55, 122.23, 122.18, 121.19, 120.03, 117.16, 116.07, 115.90, 115.21, 115.04, 113.94, 107.40, 107.33, 40.76, 40.48, 40.20, 39.93, 39.65, 39.37, 39.09.HRMS (ESI): calculated value [C 23h 14fNO 2-H] -354.0936, actual value 354.0942.
Embodiment 29
Operation steps with embodiment 1, productive rate 83%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.85 (s, 1H), 8.34 – 8.19 (m, 1H), 7.55 – 7.34 (m, 9H), 7.32 – 7.13 (m, 1H), 7.12 – 7.00 (m, 1H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 157.62,157.61,151.86,151.81,136.04,135.81,135.33,134.18,133.28,132.87,131.34,129.53,129.50,129.25,129.02,128.96,128.78,128.35,128.31,127.85,127.50,127.32,127.24,126.95,126.66,124.54,122.31,122.25,121.70,117.16,117.12,113.81,113.79,113.50,107.81,107.64,40.76,40.48,40.20,39.93,39.65,39.37,39.09.HRMS (ESI): calculated value [C 21h 13nO 2s-H] -342.0594, actual value 342.0588.
Embodiment 30
Operation steps with embodiment 1, productive rate 85%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.74 (s, 1H), 8.25 (m, 1H), 7.55 – 7.12 (m, 9H), 6.94 (m, 2H), 3.78 (m, 3H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 163.04, 162.66, 161.08, 160.73, 159.47, 158.71, 157.94, 157.88, 151.72, 151.64, 135.74, 135.54, 134.17, 133.11, 133.05, 132.70, 132.24, 131.01, 130.95, 130.28, 130.14, 130.12, 129.33, 129.25, 128.26, 128.24, 125.49, 124.51, 123.71, 122.14, 120.97, 119.14, 117.12, 116.06, 115.89, 115.18, 115.01, 114.54, 113.99, 113.82, 107.39, 107.32, 55.67, 55.46, 40.76, 40.48, 40.20, 39.93, 39.65, 39.37, 39.09.HRMS (ESI): calculated value [C 24h 16fNO 3-H] -384.1041, actual value 384.1049.
Embodiment 31
Operation steps with embodiment 1, productive rate 70%. 1hNMR (500MHz, d 6-DMSO, 298K): δ 12.48 (s, 1H), 8.19 (d, j=7.0Hz, 1H), 7.69 – 7.60 (m, 2H), 7.59 – 7.49 (m, 2H), 7.48 – 7.27 (m, 4H), 2.47 (s, 3H). 13cNMR (125MHz, d 6-DMSO, 298K): δ 158.89,151.65,135.07,133.35,131.81,130.60,129.10,128.90,128.15,127.89,124.38,121.94,117.09,115.78,114.12,108.49,40.76,40.48,40.20,39.93,39.65,39.37,39.09,10.92.HRMS (ESI): calculated value [C 18h 13nO 2-H] -274.0874, actual value 274.0872.
Embodiment 32
Operation steps with embodiment 1, productive rate 40%. 1hNMR (300MHz, d 6-DMSO, 298K): δ 13.38 (s, 1H), 8.51 (dd, j=7.8,1.2Hz, 1H), 7.63 – 7.49 (m, 1H), 7.48 – 7.24 (m, 7H), 4.15 (q, j=7.1Hz, 2H), 1.06 (t, j=7.1Hz, 3H). 13cNMR (75MHz, d 6-DMSO, 298K): δ 160.61,157.22,152.33,137.32,132.48,130.97,130.91,130.69,127.65,127.23,124.60,123.43,123.39,117.18,113.29,107.76,60.79,40.76,40.48,40.20,39.93,39.65,39.37,39.09,14.09.HRMS (ESI): calculated value [C 20h 15nO 2-H] -332.0928, actual value 332.0928.

Claims (4)

1. a synthetic method for coumarin-pyrrole compound, is characterized in that: described synthetic method is with 4-aminocoumarin compounds 1with two replaced acetylene compounds 2for raw material, its feed ratio is 1:3, is dissolved in reaction solvent, at Pd (OAc) 2the obtained corresponding target product of reaction under catalysis, oxygenant effect, described oxygenant is Cu (OAc) 2with oxygen combination, Cu (OAc) 2consumption is 0.2 equivalent of 4-aminocoumarin compounds, and described reaction solvent is N,N-dimethylacetamide, reaction process as shown in the formula (I):
Formula (I)
Wherein, R 1for hydrogen atom, methyl, ethyl, methoxyl group or halogen; R 2, R 3for the phenyl, naphthyl, thienyl, ethoxycarbonyl, methyl, the ethyl that are replaced by methyl, methoxyl group, halogen, trifluoromethyl, TMS.
2. the synthetic method of coumarin-pyrrole compound as claimed in claim 1, is characterized in that, described Pd (OAc) 2consumption is 0.1 equivalent of 4-aminocoumarin compounds.
3. the synthetic method of coumarin-pyrrole compound as claimed in claim 1, it is characterized in that, described 4-aminocoumarin compounds concentration is 0.1mmol/L, and described pair of replaced acetylene compounds concentration is 0.3mmol/L.
4. the synthetic method of coumarin-pyrrole compound as claimed in claim 1, it is characterized in that, described temperature of reaction is room temperature-120 oc.
CN201310174499.3A 2013-05-13 2013-05-13 The synthetic method of coumarin-pyrrole compound Expired - Fee Related CN103232462B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201310174499.3A CN103232462B (en) 2013-05-13 2013-05-13 The synthetic method of coumarin-pyrrole compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201310174499.3A CN103232462B (en) 2013-05-13 2013-05-13 The synthetic method of coumarin-pyrrole compound

Publications (2)

Publication Number Publication Date
CN103232462A CN103232462A (en) 2013-08-07
CN103232462B true CN103232462B (en) 2016-03-02

Family

ID=48880542

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201310174499.3A Expired - Fee Related CN103232462B (en) 2013-05-13 2013-05-13 The synthetic method of coumarin-pyrrole compound

Country Status (1)

Country Link
CN (1) CN103232462B (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103992332B (en) * 2014-06-06 2016-01-13 广西师范大学 Prepare the method for furans [3,2-C] coumarin compound
CN103992298B (en) * 2014-06-06 2015-10-28 广西师范大学 The method of synthesis 3-styrylcoumarin compounds
CN104387405B (en) * 2014-12-11 2016-06-15 长沙理工大学 A kind of method of synthesis furan [3,2-c] coumarin derivative
CN113072477B (en) * 2021-03-29 2022-07-22 郑州轻工业大学 Method for synthesizing polysubstituted pyrrole derivative

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1371371A (en) * 1999-09-03 2002-09-25 英登纳股份有限公司 Novel derivatives of flavones, xanthones and coumarins
CN1635029A (en) * 2003-12-26 2005-07-06 中国科学院理化技术研究所 Coumarin dyestuff linked by naphthene ketones, method for synthesis and use thereof
WO2009000411A1 (en) * 2007-06-26 2008-12-31 Sanofi-Aventis A transition metal catalyzed synthesis of 2h-indazoles
CN102924459A (en) * 2012-10-25 2013-02-13 华东师范大学 Synthetic method of pyrrole fused-ring 3-indolone type compounds

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1371371A (en) * 1999-09-03 2002-09-25 英登纳股份有限公司 Novel derivatives of flavones, xanthones and coumarins
CN1635029A (en) * 2003-12-26 2005-07-06 中国科学院理化技术研究所 Coumarin dyestuff linked by naphthene ketones, method for synthesis and use thereof
WO2009000411A1 (en) * 2007-06-26 2008-12-31 Sanofi-Aventis A transition metal catalyzed synthesis of 2h-indazoles
CN102924459A (en) * 2012-10-25 2013-02-13 华东师范大学 Synthetic method of pyrrole fused-ring 3-indolone type compounds

Also Published As

Publication number Publication date
CN103232462A (en) 2013-08-07

Similar Documents

Publication Publication Date Title
CN103232462B (en) The synthetic method of coumarin-pyrrole compound
Ren et al. Rhodium (III)-catalyzed [4+ 2] annulation of N-arylbenzamidines with 1, 4, 2-dioxazol-5-ones: Easy access to 4-aminoquinazolines via highly selective CH bond activation
Xu et al. Rhodium (III)-catalyzed selective access to isoindolinones via formal [4+ 1] annulation of arylamides and propargyl alcohols
Miyazaki et al. Discovery of novel dihydroimidazothiazole derivatives as p53–MDM2 protein–protein interaction inhibitors: Synthesis, biological evaluation and structure–activity relationships
He et al. Rh (III)-catalyzed CH activation of primary benzamides and tandem cyclization with cyclic 2-diazo-1, 3-diketones for the synthesis of isocoumarins
Shi et al. Concise and divergent total synthesis of swainsonine, 7-alkyl swainsonines, and 2, 8a-diepilentiginosine via a chiral heterocyclic enaminoester intermediate
Faisal et al. Review on asymmetric synthetic methodologies for chiral isoquinuclidines; 2008 to date
Arumugam et al. A facile ionic liquid-accelerated, four-component cascade reaction protocol for the regioselective synthesis of biologically interesting ferrocene engrafted spiropyrrolidine hybrid heterocycles
Yu et al. Selective synthesis of pyrazolonyl spirodihydroquinolines or pyrazolonyl spiroindolines under aerobic or anaerobic conditions
Chang et al. 1, 4-Diazabicyclo [2.2. 2] octane-Catalyzed multicomponent domino strategy for the synthesis of tetrasubstituted NH-pyrroles
CN102659494A (en) Method for asymmetric synthesis of 3,3-disubstituted-2-oxindole compound
Chen et al. BF3-promoted annulation of azonaphthalenes and ynamides for synthesis of benzo [e] indoles
Tang et al. Convenient and efficient access to tri-and tetra-substituted 4-fluoropyridines via a [3+ 2]/[2+ 1] cyclization reaction
Balwe et al. Diversity-oriented one-pot synthesis of furan based densely substituted biheteroaryls via isocyanide insertion
CN108863890A (en) A kind of 4- pyrroline-2-one derivative and preparation method thereof
Hizartzidis et al. Synthesis and Cytotoxicity of Octahydroepoxyisoindole‐7‐carboxylic Acids and Norcantharidin–Amide Hybrids as Norcantharidin Analogues
CN104557663A (en) Synthetic method of dicarbonyl substituted indole pharmaceutical intermediate compound
Kuraitheerthakumaran et al. Rapid and efficient one-pot synthesis of octahydroquinazolinone derivatives using lanthanum oxide under solvent-free condition
CN115215796B (en) Synthesis method of 3-acyl quinoline compound
Bellina et al. Synthetic applications of 3, 4-dihalo-2 (5H)-furanones: A formal total synthesis of nostoclides I and II
CN102952061B (en) N-substituted indole-diketone compound and preparation method thereof
Sun et al. Iron‐Catalyzed [4C+ 1N] Cyclization of 4‐Acetylenic Ketones with Primary Amines: Synthesis of 5‐(Aryl) alkylidene‐4, 5‐dihydropyrroles
CN107459536B (en) A kind of green synthesis method of 4- ferrocenyl quinoline
Laidaoui et al. Palladium-Catalysed Direct Heteroarylation of Bromobenzylacetamide Derivatives: A Simple Access to Heteroarylated Benzylamine Derivatives
CN105017238A (en) Method for chiral spirophosphonate catalyzed synthesis of optically active 2H-1,4-benzoxazine-2-one derivative

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20160302

Termination date: 20180513