CN109678854B - Method for synthesizing pyrido [1,2-a ] indole-6 (1H) -ketone compound by manganese catalysis - Google Patents

Method for synthesizing pyrido [1,2-a ] indole-6 (1H) -ketone compound by manganese catalysis Download PDF

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CN109678854B
CN109678854B CN201910059388.5A CN201910059388A CN109678854B CN 109678854 B CN109678854 B CN 109678854B CN 201910059388 A CN201910059388 A CN 201910059388A CN 109678854 B CN109678854 B CN 109678854B
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CN109678854A (en
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郑光范
孙佳琼
李兴伟
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Shaanxi Normal University
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    • 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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    • 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 method for synthesizing pyrido [1,2-a ] by manganese catalysis]Process for the preparation of indol-6 (1H) -ones using inexpensive, commercial Mn (CO)5Br is used as catalyst, N-pyridylpyridone compound and propiolic alcohol carbonate compound are used as raw materials to obtain pyrido [1,2-a ] under the promotion of alkali]Indole-6 (1H) -ketone skeleton compound. The method has the advantages of simple operation, easy and stable raw material preparation, adoption of non-noble metal catalyst, mild reaction conditions, wide substrate application range, high product yield (up to 91%), good selectivity, overcoming the defects of complex raw material preparation, poor raw material stability, poor atom and step economy, harsh reaction conditions and the like in the traditional method, and having good application prospect.

Description

Method for synthesizing pyrido [1,2-a ] indole-6 (1H) -ketone compound by manganese catalysis
Technical Field
The invention relates to a method for synthesizing pyrido [1,2-a ] indole-6 (1H) -ketone compounds by manganese catalysis.
Background
Indole and derivatives thereof are widely used in the fields of medicine, biology, synthetic chemistry and the like, and the search for an effective method for synthesizing an indole skeleton has become an important research field. Pyrido [1,2-a ] indol-6 (1H) -one compounds are important skeletons and useful organic synthesis intermediates, but the research on the synthesis methods is relatively few, and the development of a new method for synthesizing the compounds is expected.
C-H bond activation plays an important role in modern organic synthesis. Although the introduction of the guide group ensures the activity and selectivity of C-H bond activation, the guide group is inevitably remained in the final product, and further application of the reaction is limited. To address these problems, organic synthesizers developed a series of nucleophilic localisation groups, electrophilic localisation groups (acc. chem. res.2015,48,1007), oxidative localisation groups (chem. soc. rev.2014,43,6906) and dipolar cycloaddition localisation groups (angelw. chem., int.ed.2016,55,15351). Although the development of the novel guide group greatly promotes the C-H functionalization reaction, the development of the novel positioning group which is simpler, easier to obtain and capable of being modified is realized, and the development of the new reaction property of the common positioning group in the past is very important for realizing the traceless activation of the C-H bond and the application of the C-H bond activation in production and life.
Pyridine is the most common directing group, but has only been retained as a directing group in the past into the final product. Recently developed inexpensive metal Mn (CO)5Br catalyzed C-H bond olefination (Angew. chem. int. Ed.2017,56,6660; Angew. chem. int. Ed.2017,56,12778) and reverse charged DA reactions (chem. Rev.1986.86, 781; chem. Rec.2014,14,1070; chem. Asian J.2017,12,2142; Eur. J.org. chem.2017,46,6816) provide new ideas for the conversion of pyridine directing groups.
Disclosure of Invention
The object of the present invention is to provide a commercially available Mn (CO) at a low cost5Br is used as catalyst to synthesize pyrido [1,2-a ] with high yield and high selectivity under mild condition]A synthesis method of indole-6 (1H) -ketone compounds.
Aiming at the purposes, the technical scheme adopted by the invention is as follows: propargyl alcohol carbonate compounds shown in formula I-1 or I-2, N-pyridyl pyridone compounds shown in formula II and Mn (CO)5Adding Br and alkali into an organic solvent, reacting at 80-120 ℃ under the protection of nitrogen and in a closed condition, separating and purifying a product after the reaction is finished, and obtaining the pyrido [1,2-a ] shown as a formula III-1 or III-2]Indol-6 (1H) -ones;
Figure BDA0001953641230000021
wherein R represents methoxycarbonyl or tert-butoxycarbonyl, R1、R4Each independently represents any one of H, alkyl, alkoxy, halogen, trifluoromethyl, phenethyl, phenylpropyl, benzyloxy, anilino and aryl, R2And R3Each independently represents C1～C4Alkyl radical, R5Representative H, C1～C4Any one of alkyl, halogen and trifluoromethyl, and n is an integer of 1-4.
The aboveR1Preferably H, C1～C4Alkyl, phenyl, halophenyl, nitro-substituted phenyl, trifluoromethyl-substituted phenyl, C1～C4Any one of alkyl substituted phenyl, thienyl and phenethyl.
R mentioned above4Preferably H, C1～C4Alkyl radical, C1～C2Alkoxy, halogen, trifluoromethyl, phenyl, halophenyl, nitro-substituted phenyl, trifluoromethyl-substituted phenyl, C1～C4Any one of alkyl substituted phenyl, anilino and benzyloxy.
In the above synthesis method, the molar ratio of the N-pyridylpyridone compound to the propargyl alcohol carbonate compound is preferably 1:1.5 to 2.5.
In the above synthesis method, Mn (CO) is preferred5The adding amount of Br is 5-15% of the mol amount of the N-pyridyl pyridone compound.
In the synthesis method, the dosage of the alkali is preferably 1-4 times of the molar weight of the N-pyridyl pyridone compound, wherein the alkali is any one or two of sodium acetate, potassium acetate, triethylamine, dicyclohexylamine and triethylamine, and the mixture of the sodium acetate and the dicyclohexylamine in a molar ratio of 1:4 is preferred.
In the above synthesis method, the organic solvent is preferably any one of methyl tert-butyl ether, tetrahydrofuran, diethyl ether, methanol, dichloroethane and dioxane.
The invention has the following beneficial effects:
the invention adopts cheap commercial Mn (CO)5Br is used as catalyst, N-pyridylpyridone compound and propiolic alcohol carbonate compound which are simple and easy to obtain and relatively stable are used as raw materials to obtain pyrido [1,2-a ] with high yield and high selectivity under mild condition promoted by alkali]Indole-6 (1H) -ketone skeleton compound. The method has the advantages of simple operation, easy and stable raw material preparation, adoption of non-noble metal catalyst, mild reaction conditions, wide substrate application range, high product yield (up to 91 percent), good selectivity, and overcoming the defects of complicated raw material preparation, poor raw material stability, poor atom and step economy and reaction strips of the traditional methodAnd the parts are harsh and the like, and the method has good application prospect. In the reaction, the pyridyl is not only used as a guide group, but also used as an electron-deficient diene, and the generated high-activity allene are subjected to intramolecular DA and inverse DA reactions, so that traceless conversion of the pyridyl is realized, and a new strategy is provided for realizing traceless C-H bond functionalization.
Detailed Description
The present invention will be described in further detail with reference to examples, but the scope of the present invention is not limited to these examples.
Example 1
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000031
34.4mg (0.2mmol) of 2H- [1,2' -bipyridine were added to a pressure-resistant tube in a glove box under nitrogen protection]-2-one, 87.2mg (0.4mmol) of methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate, 5.5mg (0.02 mmol) of Mn (CO)5Br, 8.2mg (0.1mmol) of sodium acetate, 72.4mg (0.4mmol) of dicyclohexylamine and 2mL of methyl tert-butyl ether, screwing a pressure-resistant pipe, taking the pressure-resistant pipe out of a glove box, stirring at 100 ℃ for reaction for 48 hours, after the reaction is finished, performing rotary evaporation under reduced pressure to remove the methyl tert-butyl ether to obtain a crude product, and quickly passing the crude product through a column by using silica gel (petroleum ether: ethyl acetate: 10: 1-5: 1) to obtain a brown viscous liquid, wherein the yield is 72%, and the characterization data is as follows:1H NMR(400MHz,CDCl3)δ7.98(d,J＝6.5Hz,1H),7.44(q,J＝3.6Hz, 3H),7.34(dd,J＝6.6,2.9Hz,2H),7.29(dd,J＝8.6,7.0Hz,1H),6.44(d,J＝9.0Hz, 1H),6.28(dd,J＝9.4,6.4Hz,1H),5.86(dd,J＝8.1,6.4Hz,2H),1.21(s,6H)；13C NMR(100MHz,CDCl3)δ148.3,142.7,142.5,138.0,137.4,132.7,131.8,130.6,128.3, 128.1,119.9,115.8,115.7,99.6,38.6,28.3.
example 2
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000041
In this example, the methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate used in example 1 was replaced by equimolar methyl (2-methyl-4-orthofluorophenylbut-3-yn-2-ol) carbonate and the procedure was otherwise as in example 1, giving a brown oily liquid in 64% yield, characterized by:1H NMR(400MHz,CDCl3)δ7.99 (d,J＝6.5Hz,1H),7.47(ddd,J＝15.2,5.3,1.8Hz,1H),7.34-7.16(m,4H),6.45(d,J＝ 9.0Hz,1H),6.30(dd,J＝9.4,6.5Hz,1H),5.89(d,J＝9.5Hz,1H),5.83(d,J＝7.0Hz, 1H),1.24(s,3H),1.18(s,3H)；13C NMR(100MHz,CDCl3)δ161.4,160.5(d,J＝246 Hz),159.2,147.3,144.7,142.5,138.1,137.5,132.9(d,J＝3Hz),130.8(d,J＝8Hz), 125.0,123.8(d,J＝4Hz),120.3(d,J＝16Hz),120.0,116.0(d,J＝6Hz),115.8(d,J＝ 22Hz),99.1,38.5,28.4,26.7.
example 3
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000042
In this example, the same procedure as in example 1 was repeated except for using equimolar amounts of methyl (2-methyl-4-m-methylphenyl but-3-yn-2-ol) carbonate instead of the methyl (2-methyl-4-phenyl but-3-yn-2-ol) carbonate used in example 1 to give a brown oily liquid in 78% yield, as characterized by:1H NMR(400MHz,CDCl3)δ7.97 (d,J＝6.5Hz,1H),7.35-7.22(m,3H),7.14-7.12(m,2H),6.44(d,J＝9.0Hz,1H),6.28 (dd,J＝9.4,6.5Hz,1H),5.86(d,J＝8.7Hz,2H),2.41(s,3H),1.22(s,6H)；13C NMR (100MHz,CDCl3)δ161.5,148.3,142.5,142.5,138.0,137.7,137.4,132.7,132.0,131.2, 129.0,127.9,127.7,119.9,115.7,115.6,99.6,38.6,28.3,21.4.
example 4
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000051
In this example, the same procedure as in example 1 was repeated except for using equimolar amounts of methyl (2-methyl-4-p-bromophenylbut-3-yn-2-ol) carbonate instead of the methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate used in example 1 to give a brown oily liquid in 80% yield, characterized by:1H NMR(400MHz,CDCl3)δ7.99 (d,J＝6.5Hz,1H),7.60(d,J＝8.3Hz,2H),7.29(dd,J＝8.6,6.8Hz,1H),7.23(d,J＝ 8.3Hz,2H),6.45(d,J＝9.0Hz,1H),6.29(dd,J＝9.4,6.5Hz,1H),5.86(dd,J＝17.3, 8.2Hz,2H),1.21(s,6H)；13C NMR(100MHz,CDCl3)δ161.3,147.8,143.2,142.4, 137.9,137.4,132.2,131.7,131.4,130.4,122.7,120.0,116.0,99.4,38.7,28.3.
example 5
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000052
In this example, the same procedure as in example 1 was repeated except for using equimolar amounts of methyl (2-methyl-4-p-nitrophenylbut-3-yn-2-ol) carbonate instead of the methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate used in example 1, to give a brown oily liquid in 42% yield, characterized by:1H NMR(400MHz,CDCl3)δ8.34 (d,J＝8.7Hz,2H),8.05(d,J＝6.5Hz,1H),7.57(d,J＝8.7Hz,2H),7.31(dd,J＝9.0, 7.1Hz,1H),6.49(d,J＝9.0Hz,1H),6.33(dd,J＝9.4,6.6Hz,1H),5.91(d,J＝9.4Hz, 1H),5.79(d,J＝7.0Hz,1H),1.22(s,6H)；13C NMR(100MHz,CDCl3)δ161.3,148.0, 147.2,144.0,142.5,140.2,137.8,137.4,131.8,129.2,123.4,120.1,116.7,116.5,99.3, 38.8,28.4.
example 6
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000061
In this example, the same procedure as in example 1 was repeated except for using equimolar amounts of methyl (2-methyl-4-p-trifluoromethylphenylbutan-3-yn-2-ol) carbonate instead of the methyl (2-methyl-4-phenylbutan-3-yn-2-ol) carbonate used in example 1 to give a reddish brown oily liquid in a yield of 70%, characterized by:1H NMR(400MHz,CDCl3) δ8.02(d,J＝6.5Hz,1H),7.74(d,J＝8.1Hz,2H),7.50(d,J＝8.1Hz,2H),7.30(dd,J ＝9.0,7.1Hz,1H),6.47(d,J＝9.0Hz,1H),6.31(dd,J＝9.4,6.5Hz,1H),5.89(d,J＝ 9.4Hz,1H),5.80(d,J＝7.0Hz,1H),1.21(s,6H)；13C NMR(100MHz,CDCl3)δ161.4, 147.7,143.6,142.5,137.9,137.4,136.9,131.1,130.7(q,J＝33Hz),130.1,125.2(q,J＝ 4Hz),124.0(q,J＝271Hz),120.1,116.3,116.2,99.5,38.7,28.4.
example 7
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000062
In this example, equimolar amounts of [ 2-methyl-4-o- (2-methylpropan-1-en-1-yl) phenylbut-3-yn-2-ol were used]The procedure was as in example 1 except for replacing methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate used in example 1 with methyl carbonate to give a reddish brown oily liquid in 67% yield characterized by:1H NMR(600 MHz,CDCl3)δ7.96(d,J＝6.5Hz,1H),7.41(td,J＝7.5,1.5Hz,1H),7.35(d,J＝7.7 Hz,1H),7.29-7.26(m,2H),7.25(dd,J＝7.3,1.6Hz,1H),6.44(d,J＝8.6Hz,1H),6.28 (dd,J＝9.4,6.5Hz,1H),5.91-5.83(m,2H),5.73(d,J＝6.9Hz,1H),1.77(d,J＝1.1Hz, 3H),1.69(d,J＝1.1Hz,3H),1.26(s,3H),1.03(s,3H)；13C NMR(150MHz,CDCl3)δ 161.7,147.4,142.7,142.5,138.9,138.3,137.6,136.3,131.8,131.4,131.2,129.9,128.2, 125.6,123.7,119.9,115.8,115.5,99.4,38.6,28.9,26.4,26.0,19.5.
example 8
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000071
In this example, equimolar amounts of [ 2-methyl-4- (thien-2-yl) but-3-yn-2-ol were used]The procedure was as in example 1 except for replacing methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate used in example 1 with methyl carbonate to give a reddish brown oily liquid in 55% yield characterized by:1H NMR(400MHz,CDCl3)δ8.02(d,J＝6.5Hz,1H),7.48(dd,J＝5.1,1.1Hz,1H),7.34(dd,J＝9.0,7.1Hz,1H), 7.18-7.07(m,2H),6.46(d,J＝9.0Hz,1H),6.30(dd,J＝9.4,6.5Hz,1H),6.09(d,J＝ 7.0Hz,1H),5.93(d,J＝9.4Hz,1H),1.32(s,6H)；13C NMR(100MHz,CDCl3)δ161.4, 148.1,145.5,143.1,137.9,137.5,132.3,130.0,127.2,127.0,124.1,119.9,116.5,116.0, 99.5,39.0,27.9.
example 9
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000072
In this example, the same procedure as in example 1 was repeated except for using equimolar amounts of methyl (3-methyl-1-phenylhex-1-yn-3-yl) carbonate instead of the methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate used in example 1 to give a reddish brown oily liquid in 81% yield as characterized by:1H NMR(400MHz,CDCl3)δ7.97(d, J＝6.5Hz,1H),7.45(dd,J＝6.2,2.7Hz,3H),7.36-7.25(m,3H),6.44(d,J＝9.0Hz, 1H),6.37(dd,J＝9.5,6.5Hz,1H),5.83(dd,J＝16.8,8.2Hz,2H),1.58-1.54(m,1H), 1.42-1.32(m,1H),1.20(s,3H),1.12-0.99(m,2H),0.74(t,J＝7.3Hz,3H)；13C NMR (100MHz,CDCl3)δ161.5,148.3,141.7,141.6,138.4,137.4,132.9,131.6,128.4,128.1, 121.5,116.1,115.7,99.5,43.9,43.3,28.4,18.7,14.1.
example 10
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000081
In this example, the same procedure as in example 1 was repeated except for using equimolar amounts of methyl (2-methyloct-3-yn-2-yl) carbonate instead of the methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate used in example 1 to give a reddish brown oily liquid in 43% yield, characterized by:1H NMR(400MHz,CDCl3)δ7.83(d,J＝6.4 Hz,1H),7.37(dd,J＝9.0,7.1Hz,1H),6.43(d,J＝9.0Hz,1H),6.30(d,J＝7.0Hz,1H), 6.22(dd,J＝9.5,6.5Hz,1H),5.84(d,J＝9.5Hz,1H),2.77-2.66(m,2H),1.66-1.55(m, 2H),1.52-1.46(m,2H),1.41(s,6H),0.99(t,J＝7.3Hz,3H)；13C NMR(100MHz, CDCl3)δ161.7,147.3,141.6,140.7,138.2,137.3,131.5,119.9,115.7,114.4,98.1,38.0, 32.9,27.7,25.6,23.3,13.8.
example 11
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000082
In this example, the same procedure as in example 1 was repeated except for using equimolar amounts of methyl (2-methylbut-3-yn-2-yl) carbonate instead of the methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate used in example 1 to give a reddish brown oily liquid in 53% yield, characterized by:1H NMR(400MHz,CDCl3)δ7.83(dd,J＝ 6.4,1.5Hz,1H),7.36(dd,J＝9.1,7.0Hz,1H),6.58(d,J＝1.6Hz,1H),6.43(d,J＝9.0 Hz,1H),6.36-6.27(m,2H),6.01(d,J＝9.5Hz,1H),1.33(s,6H)；13C NMR(100MHz, CDCl3)δ161.7,149.1,146.5,141.3,138.1,137.7,120.7,115.8,115.5,100.2,37.4,29.9.
example 12
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000083
In this example, the same procedure as in example 1 was repeated except for using equimolar amounts of methyl (2-methyl-6-phenylhex-3-yn-2-yl) carbonate instead of the methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate used in example 1 to give a reddish brown oily liquid in 53% yield as characterized by:1H NMR(400MHz,CDCl3)δ7.88(d, J＝6.5Hz,1H),7.40(dd,J＝9.0,7.1Hz,1H),7.36-7.30(m,2H),7.26–7.22(m,3H), 6.46(d,J＝9.0Hz,1H),6.36(d,J＝7.0Hz,1H),6.24(dd,J＝9.5,6.5Hz,1H),5.85(d, J＝9.4Hz,1H),3.09-3.01(m,2H),2.94-2.90(m,2H),1.39(s,6H)；13C NMR(100 MHz,CDCl3)δ161.7,147.0,141.7,141.5,141.0,138.1,137.3,130.1,128.7,128.2, 126.5,119.9,115.9,114.8,98.1,38.0,36.7,28.1,27.6.
example 13
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000091
In this example, equimolar amounts of 3-methyl-2H- [1,2' -bipyridine were used]-2-Ketone instead of 2H- [1,2' -bipyridine used in example 1]-2-ketone, the other steps being identical to those of example 1, giving a reddish brown oily liquid in a yield of 75%, characterized by:1H NMR(600MHz,CDCl3)δ7.91(d,J＝6.5Hz,1H),7.47-7.41 (m,3H),7.36-7.31(m,2H),7.16(dd,J＝7.1,0.9Hz,1H),6.26(dd,J＝9.4,6.5Hz,1H), 5.81-5.77(m,2H),2.25(s,3H),1.20(s,6H)；13C NMR(150MHz,CDCl3)δ161.58, 146.30,141.66,141.53,138.24,135.13,132.93,131.82,130.57,128.16,127.99,124.89, 119.95,114.57,99.41,38.47,28.45,16.60.
example 14
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000092
In this example, equimolar amounts of 3-methoxy-2H- [1,2' -bipyridine were used]-2-Ketone instead of 2H- [1,2' -bipyridine used in example 1]-2-ketone, the other steps being identical to those of example 1, giving a reddish brown oily liquid in 89% yield, characterized by the following:1H NMR(600MHz,CDCl3)δ7.81(d,J＝6.5Hz,1H), 7.52-7.40(m,3H),7.37-7.30(m,2H),6.63(d,J＝7.8Hz,1H),6.23(dd,J＝9.4,6.5Hz, 1H),5.75(dd,J＝12.2,8.6Hz,2H),3.85(s,3H),1.18(s,6H)；13C NMR(150MHz, CDCl3)δ156.30,146.82,141.00,140.84,140.50,138.26,132.96,131.70,130.53, 128.13,127.97,119.86,113.68,111.89,98.16,56.34,38.38,28.65.
example 15
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000101
In this example, equimolar amounts of 3-bromo-2H- [1,2' -bipyridine were used]-2-Ketone instead of 2H- [1,2' -bipyridine used in example 1]-2-ketone, the other steps being identical to those of example 1, giving a reddish brown oily liquid in 61% yield characterized by:1H NMR(600MHz,CDCl3)δ8.05(d,J＝6.5Hz,1H),7.68(d, J＝7.7Hz,1H),7.45(dd,J＝6.3,3.7Hz,3H),7.33(dd,J＝6.5,3.0Hz,2H),6.31(dd,J ＝9.4,6.6Hz,1H),5.93(d,J＝9.4Hz,1H),5.77(d,J＝7.7Hz,1H),1.21(s,6H)；13C NMR(150MHz,CDCl3)δ157.0,147.9,143.5,143.0,139.3,138.2,132.3,131.7,130.6, 128.5,128.2,120.0,117.3,110.8,99.6,39.0,28.1.
example 16
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000102
In this example, equimolar amounts of 3-phenyl-2H- [1,2' -bipyridine were used]-2-Ketone instead of 2H- [1,2' -bipyridine used in example 1]-2-ketone, the other steps being identical to those of example 1, giving a reddish brown oily liquid in 80% yield, characterized by:1H NMR(600MHz,CDCl3)δ8.07(d,J＝6.5Hz,1H),7.72(d, J＝7.2Hz,2H),7.49-7.44(m,4H),7.41(t,J＝7.7Hz,2H),7.39-7.36(m,2H),7.31(t,J ＝7.4Hz,1H),6.30(dd,J＝9.4,6.6Hz,1H),5.97(d,J＝7.4Hz,1H),5.88(d,J＝9.4 Hz,1H),1.23(s,6H)；13C NMR(150MHz,CDCl3)δ160.2,147.5,143.1,142.5,138.5, 137.3,136.0,132.8,131.7,130.7,129.0,128.4,128.2,127.3,126.9,120.1,116.0,100.1, 38.8,28.4.
example 17
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000111
In this example, equimolar amounts of 3-trifluoromethyl-2H- [1,2' -bipyridine were used]-2-Ketone instead of 2H- [1,2' -bipyridine used in example 1]-2-ketone, the other steps being identical to those of example 1, giving a reddish brown oily liquid in 80% yield, characterized by:1H NMR(600MHz,CDCl3)δ8.16(d,J＝6.6Hz,1H),7.68 (d,J＝7.6Hz,1H),7.50-7.43(m,3H),7.36-7.30(m,2H),6.35(dd,J＝9.4,6.6Hz,1H), 6.02(d,J＝9.4Hz,1H),5.91(d,J＝7.6Hz,1H),1.23(s,6H)；13C NMR(150MHz, CDCl3)δ157.4,151.1,145.8,144.7,137.6,136.6(q,J＝5Hz),132.0,131.4,130.6, 129.9(q,J＝5Hz),128.7,128.3,123.6(q,J＝269Hz),120.0,119.3,97.7,39.2,27.9.
example 18
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000112
In this example, equimolar amounts of 3-anilino-2H- [1,2' -bipyridine are used]-2-Ketone instead of 2H- [1,2' -bipyridine used in example 1]-2-ketone, the other steps being identical to those of example 1, giving a reddish brown oily liquid with a yield of 52%, characterized by:1H NMR(600MHz,CDCl3)δ7.70(d,J＝6.5Hz,1H), 7.48-7.39(m,3H),7.39-7.33(m,2H),7.31(t,J＝7.9Hz,2H),7.18(d,J＝7.8Hz,2H), 7.11(s,1H),7.08(d,J＝7.8Hz,1H),6.97(t,J＝7.3Hz,1H),6.25(dd,J＝9.4,6.5Hz, 1H),5.82(d,J＝7.8Hz,1H),5.75(d,J＝9.4Hz,1H),1.19(s,6H)；13C NMR(150 MHz,CDCl3)δ156.6,141.4,140.8,138.7,138.5,138.2,133.2,132.5,130.8,130.6, 129.4,128.1,128.0,121.9,119.9,119.0,112.8,109.8,100.6,38.4,29.0.
example 19
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000121
In this example, equimolar amounts of 4-benzyloxy-2H- [1,2' -bipyridine were used]-2-Ketone instead of 2H- [1,2' -bipyridine used in example 1]-2-ketone, the other steps being identical to those of example 1, giving a reddish brown oily liquid with a yield of 73%, characterized by:1H NMR(600MHz,CDCl3)δ7.81(d,J＝6.5Hz,1H), 7.43-7.40(m,3H),7.36-7.33(m,4H),7.32-7.20(m,3H),6.24(dd,J＝9.4,6.5Hz,1H), 5.91(d,J＝2.2Hz,1H),5.79(d,J＝9.4Hz,1H),5.61(d,J＝2.2Hz,1H),4.99(s,2H), 1.20(s,6H)；13C NMR(150MHz,CDCl3)δ166.7,162.5,148.6,144.1,141.5,137.8, 135.5,132.6,131.6,130.6,130.3,128.7,128.4,128.3,128.1,127.7,127.6,119.8,114.0, 94.7,93.8,70.4,38.6,28.4.
example 20
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000122
In this example, 5- (2-methylpropan-1-en-1-yl) -2H- [1,2' -bipyridine is used in equimolar amounts]-2-Ketone instead of 2H- [1,2' -bipyridine used in example 1]-2-ketone, the other steps being identical to those of example 1, giving a reddish brown oily liquid in 44% yield, characterized by the following:1H NMR(400MHz,CDCl3)δ8.02(d,J＝6.4 Hz,1H),7.38-7.36(m,2H),7.29-7.20(m,2H),7.11(d,J＝8.6Hz,1H),6.44(d,J＝8.9 Hz,1H),6.27(dd,J＝9.4,6.1Hz,1H),5.81(d,J＝9.4Hz,1H),5.14(s,1H),1.51(d,J ＝1.0Hz,3H),1.28(d,J＝1.2Hz,3H),1.16(s,6H)；13C NMR(100MHz,CDCl3)δ 142.4,142.3,142.1,141.4,137.7,135.5,134.7,132.8,130.9,127.9,127.5,120.3,120.0, 115.32,115.3,113.0,38.7,28.1,25.5,19.1.
example 21
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000131
In this example, equimolar amounts of 5 '-chloro-2H- [1,2' -bipyridine were used]-2-Ketone instead of 2H- [1,2' -bipyridine used in example 1]-2-ketone, the other steps being identical to those of example 1, giving a reddish brown oily liquid in 59% yield characterized by:1H NMR(600MHz,CDCl3)δ7.85(d,J＝7.2Hz,1H),7.51-7.42 (m,3H),7.34-7.28(m,3H),6.52-6.40(m,2H),5.84(d,J＝7.0Hz,1H),1.39(s,6H)；13C NMR(150MHz,CDCl3)δ161.3,148.4,145.7,142.6,137.6,137.3,132.4,132.3, 130.5,128.6,128.3,121.4,116.4,114.6,100.3,43.5,27.5.
example 22
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000132
In this example, 5 '-trifluoromethyl-2H- [1,2' -bipyridine is used in equimolar amounts]-2-Ketone instead of 2H- [1,2' -bipyridine used in example 1]-2-ketone, the other steps being identical to those of example 1, giving a reddish brown oily liquid in 48% yield, characterized by the following:1H NMR(600MHz,CDCl3)δ7.88(d,J＝6.8Hz,1H), 7.51-7.44(m,3H),7.35-7.27(m,3H),6.94(dd,J＝7.1,1.5Hz,1H),6.48(d,J＝9.0Hz, 1H),5.82(d,J＝6.9Hz,1H),1.42(s,6H)；13C NMR(150MHz,CDCl3)δ161.2,148.6, 142.4,140.6,138.0,135.4(q,J＝26Hz),132.8,132.2,130.3,128.7,128.4,126.2(q,J＝ 6Hz),124.4(q,J＝272Hz),117.6,111.2,101.2,39.8,27.6.
example 23
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000133
In this example, equimolar amounts of 4 '-methyl-2H- [1,2' -bipyridine were used]-2-Ketone instead of 2H- [1,2' -bipyridine used in example 1]-2-ketone, the other steps being identical to those of example 1, giving a reddish brown oily liquid in a yield of 72%, characterized by the following:1H NMR(600MHz,CDCl3)1H NMR(600MHz,CDCl3)δ 7.90(s,1H),7.47-7.42(m,3H),7.34-7.22(m,2H),7.31-7.26(m,1H),6.44(d,J＝8.9 Hz,1H),5.85(d,J＝7.0Hz,1H),5.57(s,1H),2.02(d,J＝1.3Hz,3H),1.18(s,6H)；13C NMR(150MHz,CDCl3)δ161.5,148.6,142.8,138.2,137.7,137.4,132.9,131.4,130.6, 128.3,128.1,127.7,119.6,115.7,99.6,38.2,28.5,21.6.
example 24
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000141
In this example, an equimolar amount of [1- (phenylethynyl) cyclopentyl ] was used]The procedure was as in example 1 except for replacing methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate used in example 1 with methyl carbonate to give a reddish brown oily liquid in 80% yield characterized by:1H NMR(400MHz,CDCl3)δ8.01(d,J＝6.4 Hz,1H),7.48-7.39(m,3H),7.36-7.31(m,2H),7.27(dd,J＝5.9,2.9Hz,1H),6.43(d,J ＝9.0Hz,1H),6.24(dd,J＝9.4,6.5Hz,1H),6.09(d,J＝9.4Hz,1H),5.82(d,J＝7.0 Hz,1H),2.03-1.93(m,2H),1.85-1.78(m,2H),1.71-1.62(m,2H),1.42-1.35(m,2H)；13C NMR(100MHz,CDCl3)δ161.4,148.5,143.2,141.2,138.5,137.4,132.7,131.0, 130.6,128.2,118.2,115.9,115.6,99.5,48.6,42.0,26.0.
example 25
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000142
In this example, an equimolar amount of [1- (phenylethynyl) cycloheptyl group was used]The procedure was as in example 1 except for replacing methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate used in example 1 with methyl carbonate to give a reddish brown oily liquid in 73% yield characterized by:1H NMR(400MHz,CDCl3)δ7.97(d,J＝6.1 Hz,1H),7.50-7.40(m,3H),7.34-7.31(m,2H),7.26(t,J＝8.8Hz,1H),6.43-6.32(m, 3H),5.78(d,J＝7.0Hz,1H),1.97-1.86(m,2H),1.69-1.64(m,2H),1.58-1.44(m,4H), 1.40-1.28(m,4H)；13C NMR(100MHz,CDCl3)δ148.6,145.1,140.3,138.0,137.4, 133.2,131.4,130.8,128.2,128.1,120.4,115.7,115.4,99.6,45.7,40.5,28.6,23.9.
example 26
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000151
In this example, equimolar of [1- (ethynyl) cycloheptyl was used]The procedure was as in example 1 except for replacing methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate used in example 1 with methyl carbonate to give a reddish brown oily liquid in 91% yield characterized by:1H NMR(400MHz,CDCl3)δ7.82(d,J＝6.2 Hz,1H),7.35(dd,J＝8.9,7.1Hz,1H),6.60(s,1H),6.54(d,J＝9.7Hz,1H),6.45-6.30 (m,3H),1.85-1.78(m,1H),1.74-1.68(m,6H),1.63-1.54(m,2H),1.51-1.46(m,1H)；13C NMR(100MHz,CDCl3)δ161.7,149.8,146.5,138.5,138.3,137.7,121.5,116.2, 115.5,115.0,100.0,41.0,39.5,25.6,21.4.
example 27
To prepare a pyrido [1,2-a ] indol-6 (1H) -one skeleton compound with the structural formula
Figure BDA0001953641230000152
In this example, 5 '-methyl-2H- [1,2' -bipyridine is used in equimolar amounts]-2-Ketone instead of 2H- [1,2' -bipyridine used in example 1]-2-one with equimolar [1- (phenylethynyl) cyclopentyl group]The procedure was as in example 1 except for replacing methyl (2-methyl-4-phenylbut-3-yn-2-ol) carbonate used in example 1 with methyl carbonate to give a reddish brown oily liquid in 76% yield characterized by:1H NMR(400MHz,CDCl3)δ7.93 (s,1H),7.49-7.38(m,3H),7.36-7.30(m,2H),7.27(dd,J＝5.7,3.3Hz,1H),6.43(d,J ＝8.9Hz,1H),5.82(d,J＝7.2Hz,2H),2.02(d,J＝1.3Hz,3H),2.00-1.91(m,2H), 1.82-1.74(m,2H),1.67-1.63(m,2H),1.43-1.32(m,2H)；13C NMR(100 MHz,CDCl3) δ161.5,148.8,143.2,138.7,137.4,136.3,132.8,130.6,130.5,128.2,128.2,125.9, 119.8,115.4,99.5,48.2,42.0,25.9,21.7. 。

Claims (5)

1. manganese-catalyzed synthesis of pyrido [1,2-a]A process for the preparation of indol-6 (1H) -ones, which comprises: propargyl alcohol carbonate compounds shown in formula I-1 or I-2, N-pyridyl pyridone compounds shown in formula II and Mn (CO)5Br and alkali are added into an organic solvent to react at 80-120 ℃ under the protection of nitrogen and in a closed condition, and the product is separated and purified after the reaction is finished to obtain pyrido [1,2-a]Indol-6 (1H) -ones;
Figure DEST_PATH_IMAGE001
Figure 771755DEST_PATH_IMAGE002
wherein R represents methoxycarbonyl or tert-butoxycarbonyl, R1Representative H, C1～C4Alkyl, phenyl, halophenyl, nitro-substituted phenyl, trifluoromethyl-substituted phenyl, C1～C4Any one of alkyl substituted phenyl, thienyl and phenethyl, R2And R3Each independently represents C1～C4Alkyl radical, R4Representative H, C1～C4Alkyl radical, C1～C2Alkoxy, halogen, trifluoromethyl, phenyl, halophenyl, nitro-substituted phenyl, trifluoromethyl-substituted phenyl, C1～C4Any one of alkyl substituted phenyl, anilino and benzyloxy, R5Representative H, C1～C4Any one of alkyl, halogen and trifluoromethyl, and n is an integer of 1-4;
the alkali is any one or two of sodium acetate, potassium acetate, triethylamine, dicyclohexylamine and triethylamine;
the organic solvent is any one of methyl tert-butyl ether, tetrahydrofuran, diethyl ether, methanol, dichloroethane and dioxane.
2. The manganese-catalyzed synthesis of pyrido [1,2-a]A process for the preparation of indol-6 (1H) -ones, which comprises: the molar ratio of the N-pyridyl pyridone compound to the propargyl alcohol carbonate compound is 1: 1.5-2.5.
3. The manganese-catalyzed synthesis of pyrido [1,2-a]A process for the preparation of indol-6 (1H) -ones, which comprises: the Mn (CO)5The adding amount of Br is 5-15% of the mol amount of the N-pyridyl pyridone compound.
4. The manganese-catalyzed synthesis of pyrido [1,2-a]A process for the preparation of indol-6 (1H) -ones, which comprises: the dosage of the alkali is 1-4 times of the molar weight of the N-pyridyl pyridone compound.
5. The manganese-catalyzed synthesis of pyrido [1,2-a]A process for the preparation of indol-6 (1H) -ones, which comprises: the alkali is a mixture of sodium acetate and dicyclohexylamine with the molar ratio of 1: 4.
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