CN107868093A - A kind of method for preparing 1,4 oxygen Azepinoindole analog derivatives - Google Patents

A kind of method for preparing 1,4 oxygen Azepinoindole analog derivatives Download PDF

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CN107868093A
CN107868093A CN201710839849.1A CN201710839849A CN107868093A CN 107868093 A CN107868093 A CN 107868093A CN 201710839849 A CN201710839849 A CN 201710839849A CN 107868093 A CN107868093 A CN 107868093A
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oxygen
azepinoindole
nitrae
analog derivative
rhodium
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王杭祥
马学骥
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Zhejiang University ZJU
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Zhejiang University ZJU
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems

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Abstract

The invention discloses a kind of method for preparing Isosorbide-5-Nitrae oxygen Azepinoindole analog derivative, in organic solvent; make catalyst with the rhodium of tetrabasic carboxylic acid two, with N sulfonyls 1,2; 3 triazole class compounds and the ketone derivatives of 3 methylene indoles 2 are substrate, synthesize Isosorbide-5-Nitrae oxygen Azepinoindole analog derivative.The inventive method method for preparing raw material is simple, easily preserves, with a small amount of commodity rhodium catalyst, can substantially reduce cost.The inventive method can be used for synthesizing a series of Isosorbide-5-Nitrae oxygen Azepinoindole analog derivatives, and the product of synthesis has potential bioactivity.

Description

A kind of method for preparing Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative
Technical field
The present invention relates to organic synthesis field, and in particular to a kind of side for preparing Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative Method.
Background technology
Isosorbide-5-Nitrae-oxygen azatropylidene class and cycle compound are a kind of important organic heterocyclic molecules, medicine, herbicide and There is important application in bactericide, as such compound reserpine Central nervous system of Clinical practice has lasting stabilize Effect, is a kind of good sedative；Enrico Garattini groups (Antiproliferative and differentiating activities of a novel series of histone deacetylase Inhibitors.ACS Med.Chem.Lett., 2010,1,411-415.) systematically investigate a series of 1,4- oxygen azatropylidenes Class and antitumor activity of the cycle compound as histidine deacerylase inhibitors；In addition, Isosorbide-5-Nitrae-oxygen azatropylidene class and cycle compound Important concern (Process development and scale-up of a are also received as phosphokinase inhibitor benzoxazepine-containing kinase inhibitor.Org.Process Res.Dev.,2015,19,721– 734.).But at present, the research of such compound is mostly focused on phendioxin, 4- oxygen azatropylidene analog derivatives.To adapt to drug sieve Choosing and the research of structure-activity relationship are, it is necessary to establish Isosorbide-5-Nitrae-oxygen azatropylidene class and cycle compound storehouse, wherein Isosorbide-5-Nitrae-oxygen Azepinoindole Analog derivative is important part, and developing the method for efficiently synthesizing such compound has important meaning.
The method of traditional synthesis Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative is with 2-, or the indoles of 3- substitutions is original Material, by intramolecular annulation build Isosorbide-5-Nitrae-oxygen azatropylidene ring structure (Org.Lett., 2016,18,380-383； Org.Lett.,2009,11,5494-5497；J.Org.Chem.,2016,81,10392-10403；Org.Lett.,2010, 12,192-195.).But the universal process of synthesis of raw material is more complicated, and on newly-generated oxygen azatropylidene ring introduce substituent compared with It is difficult.
In recent years, N- sulfonyls -1,2,3-triazoles can be obtained by the cycloaddition reaction of the Terminal Acetylenes and sulfonyl nitrine of copper catalysis Arrive, high income, reaction condition is gentle, easy to operate (Efficient Synthesis of 1-Sulfonyl-1,2,3- triazoles.Org.Lett.2010,12,4952–4955).Transition metal rhodium (II) catalyst can be catalyzed the open loop of triazole Denitrogenation forms active α-imido grpup metal carbene intermediate, and the synthesis of heterocycle is participated in as novel C-C-N ternarys synthon (Chem.Soc.Rev.2014,43,5151-5162；Chem.–Eur.J.2016,50,17910-17924.).By rhodium catalysis N- sulfonyls -1,2,3-triazoles class compound synthesis Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative has no report.
The content of the invention
The invention provides a kind of method for preparing Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative of rhodium catalysis of tetrabasic carboxylic acid two, Raw material is easy to get, and preparation method is simple.
One kind prepares Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative method, including：In organic solvent environment, tetrabasic carboxylic acid is used Two rhodiums make catalyst, using N- sulfonyls -1,2,3-triazoles class compound and 3- methylene indol-2-one derivatives as the step of raw material one Compound of the synthesis with following chemical formula (I)：
Described N- sulfonyl -1,2,3- triazole class compounds have the structure shown in chemical formula (II)：
Described 3- methylene indol-2-one derivatives have the structure shown in chemical formula (III)：
In chemical formula (I)~(III), R1The alkyl for the saturation for being 1~12 for carbon number, aryl, substituted aryl, heteroaryl Base；R2The alkyl for the saturation for being 1~6 for aryl, substituted aryl or carbon number；R3For aryl, substituted aryl, heteroaryl or carbon Atomicity is the alkyl of 1~6 saturation；R4Alkyl, halogen atom, methoxyl group and the ester group for the saturation for being 1~6 for H, carbon number Deng；Wherein, R1And R3In aryl on substituent independently selected from halogen (be preferably F, Cl, Br, I), CF3、CN、C1~C5Alkane Base or C1~C4Alkanoyl or C1~C4Alkoxy.
Preferably, described aryl is phenyl；Described heteroaryl is thienyl or furyl.
Preferably, R1And R3In aryl on substituent independently selected from halogen atom (be preferably F, Cl, Br), CF3, CN, alkyl or formoxyl.
Preferably, R in described N- sulfonyls -1,2,3-triazoles class compound1For electrophilic group, 3- methylene Yin In diindyl -2- ketone derivatives on phenyl ring 5- substds to improve reaction yield.
Preferably, the R1Preferably phenyl, substituted-phenyl, thienyl, C1~C5Alkyl, wherein the substituent selects From C1~C5Alkyl, F, CF3、C1~C3Alkanoyl, C1~C3Alkoxy.More preferably, phenyl, fluorine substituted-phenyl, trifluoro Methyl substituted-phenyl, formoxyl substituted-phenyl, amyl group substituted-phenyl, methoxy substitution phenyl, butyl, thienyl.
Preferably, the R2Preferably phenyl, methyl substituted-phenyl；More preferably, to methyl substituted-phenyl.
Preferably, the R3Preferably phenyl, substituted-phenyl, wherein substituent are F, Cl, Br, I；More preferably Phenyl, the phenyl of F substitutions.
Preferably, the R4Preferably H, C1~C3Alkoxy；More preferably H or methoxyl group.
In the present invention, described N- sulfonyls -1,2,3-triazoles class compound is spread out with described 3- methylene indol-2-ones The mol ratio of biology is 1:1~4:1；Further preferred mol ratio is 1:1~2:1；The described rhodium catalyst of tetrabasic carboxylic acid two with The mol ratio of described N- sulfonyl -1,2,3- triazole class compounds is 0.005~0.04:1, to improve the yield of reaction.
In the present invention, catalyst amount used is smaller, and the described rhodium catalyst of tetrabasic carboxylic acid two is the rhodium of tetraacethyl two, four pungent Sour two rhodiums, the rhodium of four pivalic acid two, four [N- phthalyls-(S)-valine)] two rhodium [Rh2(S-PTV)4] in one kind or more Kind；The more preferably rhodium of four pivalic acid two or four [N- phthalyls-(S)-valine)] two rhodium [Rh2(S-PTV)4]。
In the present invention, the temperature of described synthesis is 80~140 DEG C；The time of described synthesis is 1~6h.Ordinary circumstance Under, the reaction time is that substrate can be made to convert completely in 3 hours, the low substrate of a small number of activity, the proper extension reaction time.Reaction temperature Height is spent, the reaction time is long, is unfavorable for the practical application of reaction, the temperature of described synthesis is preferably 80~140 DEG C, enters one Step is preferably 90~100 DEG C, more preferably 95 DEG C.
In the present invention, described organic solvent is dichloromethane, chloroform, toluene, ethyl acetate, 1,2- dichloroethanes In one or more, preferably 1,2- dichloroethanes.
In the present invention, the reaction equation of described synthesis is：
Wherein, R1Alkyl, aryl, substituted aryl, the heteroaryl for the saturation for being 1~12 for carbon number；R2For aryl, take For the alkyl for the saturation that aryl or carbon number are 1~6；R3It is 1~6 for aryl, substituted aryl, heteroaryl or carbon number The alkyl of saturation；R4Alkyl, halogen atom, methoxyl group and ester group of the saturation for being 1~6 for H, carbon number etc.；Wherein, R1And R3 In aryl on substituent independently selected from halogen, CF3、CN、C1~C5Alkyl or C1~C4Alkanoyl or C1~C4Alkoxy.
Compared with prior art, the present invention has advantages below：
The inventive method is reacted with N- sulfonyls -1,2,3-triazoles class compound and 3- methylene indol-2-one derivatives Pyrrolo-indole analog derivative is obtained, raw material is cheap and easy to get, and preparation method is simple, and rhodium catalyst dosage is few, can substantially reduce into This.The inventive method can be used for synthesizing a series of Isosorbide-5-Nitraes-oxygen Azepinoindole analog derivative, and the product of synthesis has potential life Thing activity.
Embodiment
The present invention is described in detail with reference to embodiment, but the present invention is not limited to this.
In the dry pressure-resistant reaction tubes of 15mL, 90mg 4- phenyl-N- p-toluenesulfonyls -1,2, the nitrogen of 3- tri- are added Azoles, 44mg 3- benzylideneis indol-2-one, 9.9mg four [N- phthalyls-(S)-valine)] two rhodiums and 1.0mL 1,2- dichloroethanes.Under a nitrogen, 95 DEG C of stirring reactions 3 hours.Reaction end is cooled to room temperature, directly crosses silicagel column (oil The volume ratio of ether and ethyl acetate is 10:1) product 43mg, is obtained, yield 44%, course of reaction is shown below：
The product that the present embodiment is prepared carries out nuclear magnetic resonance and mass spectral analysis：
1H NMR(600MHz,CDCl3):δ=10.12 (s, 1H), 7.82 (d, J=7.8Hz, 2H), 7.57 (d, J= 7.8Hz, 1H), 7.46 (t, J=7.2Hz, 1H), 7.25 (d, J=7.8Hz, 2H), 7.22 (d, J=7.8Hz, 1H), 7.03- 7.07(m,2H),7.00-7.03(m,2H),6.89-6.94(m,7H),4.97(s,1H),3.32(s,1H),2.39(s,3H)；
13C NMR(150MHz,CDCl3):δ=174.3,145.9,145.5,144.0,142.2,137.2,136.5, 132.9,129.6,129.5,129.3,127.7,127.4,127.3,127.0,126.9,126.5,123.2,123.1, 121.5,113.8,93.2,56.0,21.6；
HRMS(ESI,m/z):calcd.for C30H25N2O3S+(M+H)+:requires 493.1580,found: 493.1582.
Embodiment 2
In the dry pressure-resistant reaction tubes of 15mL, 96mg 4- (4- fluorophenyls)-N- p-toluenesulfonyls -1,2,3- are added Triazole, 44mg 3- (benzylidenei) indol-2-one, 9.9mg four [N- phthalyls-(S)-valine)] two rhodiums and 1.0mL 1,2- dichloroethanes.Under a nitrogen, 95 DEG C of stirring reactions 3 hours.Reaction end is cooled to room temperature, directly crosses silica gel (volume ratio of petroleum ether and ethyl acetate is 10 to post:1) product 60mg, is obtained, yield 59%, course of reaction is shown below：
The product that the present embodiment is prepared carries out nuclear magnetic resonance and mass spectral analysis：
1H NMR(600MHz,CDCl3):δ=10.10 (s, 1H), 7.82 (d, J=8.4Hz, 2H), 7.58 (d, J= 8.4Hz, 1H), 7.47 (t, J=7.8Hz, 1H), 7.27 (d, J=8.4Hz, 2H), 7.23 (d, J=8.4Hz, 1H), 7.02- 7.06 (m, 4H), 6.86-6.89 (m, 4H), 6.58 (t, J=8.4Hz, 2H), 4.96 (s, 1H), 3.37 (s, 1H), 2.40 (s, 3H)；
13C NMR(150MHz,CDCl3):δ=173.7,145.9,145.6,144.1,138.2,137.0,136.3, 132.7,129.6,129.2,128.3,128.2,127.9,127.1,127.0,123.2,123.1,121.6,114.2, 114.0,113.8,92.8,56.0,21.6；
HRMS(ESI,m/z):calcd.for C30H24FN2O3S+(M+H)+:requires 511.1486,found: 511.1489.
Embodiment 3
In the dry pressure-resistant reaction tubes of 15mL, 110mg 4- (4- trifluoromethyl bases phenyl)-N- tolysulfonyl is added Base -1,2,3- triazoles, 44mg 3- (benzylidenei) indol-2-one, 9.9mg four [N- phthalyls-(S)-figured silk fabrics ammonia Acid)] two rhodiums and 1.0mL 1,2- dichloroethanes.Under a nitrogen, 95 DEG C of stirring reactions 3 hours.Reaction end is cooled to room temperature, Directly crossing silicagel column, (volume ratio of petroleum ether and ethyl acetate is 10:1) product 55mg, is obtained, yield 49%, course of reaction is such as Shown in following formula：
The product that the present embodiment is prepared carries out nuclear magnetic resonance and mass spectral analysis：
1H NMR(600MHz,CDCl3):δ=10.13 (s, 1H), 7.81 (d, J=7.8Hz, 2H), 7.59 (d, J= 8.4Hz, 1H), 7.49 (t, J=7.8Hz, 1H), 7.27 (d, J=7.8Hz, 2H), 7.25 (d, J=7.8Hz, 1H), 7.14 (d, J=7.8Hz, 2H), 7.18 (t, J=7.8Hz, 1H), 7.00-7.05 (m, 5H), 6.87 (d, J=7.8Hz, 2H), 5.00 (s, 1H),3.45(s,1H),2.40(s,3H)；
13C NMR(150MHz,CDCl3):δ=173.1,146.2,145.9,145.6,144.2,136.9,135.9, 132.7,129.8,129.7,129.1,128.0,127.3,127.1,126.8,124.2,124.1,123.2,123.0, 121.7,113.9,92.9,56.0,21.6；
HRMS(ESI,m/z):calcd.for C31H24F3N2O3S+(M+H)+:requires 561.1454,found: 561.1450.
Embodiment 4
In the dry pressure-resistant reaction tubes of 15mL, 102mg 4- (4- acetyl phenyl)-N- tolysulfonyl -1,2 is added, 3- triazoles, 44mg 3- (benzylidenei) indol-2-one, 9.9mg four [N- phthalyls-(S)-valine)] two rhodiums and 1.0mL 1,2- dichloroethanes.Under a nitrogen, 95 DEG C of stirring reactions 3 hours.Reaction end is cooled to room temperature, directly crosses silica gel (volume ratio of petroleum ether and ethyl acetate is 10 to post:1) product 51mg, is obtained, yield 48%, course of reaction is shown below：
The product that the present embodiment is prepared carries out nuclear magnetic resonance and mass spectral analysis：
1H NMR(600MHz,CDCl3):δ=10.14 (s, 1H), 7.81 (d, J=7.8Hz, 2H), 7.59 (d, J= 8.4Hz, 1H), 7.47-7.49 (m, 3H), 7.23-7.27 (m, 3H), 7.07-7.09 (t, J=7.2Hz, 1H), 7.00-7.04 (m, 5H), 6.91 (d, J=6.0Hz, 2H), 5.01 (s, 1H), 3.47 (s, br, 1H), 2.42 (s, 3H), 2.39 (s, 3H)；
13C NMR(150MHz,CDCl3):δ=197.7,173.3,147.5,145.9,145.6,144.2,136.9, 135.9,135.8,132.7,129.8,129.6,129.1,127.9,127.4,127.2,127.1,126.6,123.2, 123.0,121.7,113.9,93.0,56.0,26.5,21.6；
HRMS(ESI,m/z):calcd.for C32H27N2O4S+(M+H)+:requires 535.1686,found: 535.1690.
Embodiment 5
In the dry pressure-resistant reaction tubes of 15mL, 111mg 4- (4- amyl groups phenyl)-N- tolysulfonyl -1,2 is added, 3- triazoles, 44mg 3- (benzylidenei) indol-2-one, 9.9mg four [N- phthalyls-(S)-valine)] two rhodiums and 1.0mL 1,2- dichloroethanes.Under a nitrogen, 95 DEG C of stirring reactions 3 hours.Reaction end is cooled to room temperature, directly crosses silica gel (volume ratio of petroleum ether and ethyl acetate is 10 to post:1) product 52mg, is obtained, yield 46%, course of reaction is shown below：
The product that the present embodiment is prepared carries out nuclear magnetic resonance and mass spectral analysis：
1H NMR(400MHz,CDCl3):δ=10.10 (s, 1H), 7.83 (d, J=8.4Hz, 2H), 7.57 (d, J= 8.4Hz, 1H), 7.45 (t, J=7.2Hz, 1H), 7.26 (d, J=8.4Hz, 2H), 7.20 (d, J=8.4Hz, 1H), 6.97- 7.06 (m, 4H), 6.87 (d, J=7.2Hz, 2H), 6.78 (d, J=8.4Hz, 2H), 6.68 (d, J=8.4Hz, 2H), 4.94 (s, 1H), 3.30 (s, 1H), 2.39 (s, 3H), 2.35 (t, J=7.2Hz, 2H), 1.34-1.42 (m, 2H), 1.21-1.26 (m, 2H), 1.06-1.12 (m, 2H), 0.84 (t, J=7.2Hz, 3H)；
13C NMR(100MHz,CDCl3):δ=174.5,145.9,145.4,143.9,142.2,139.5,137.2, 136.6,132.9,129.6,129.4,129.3,127.6,127.3,127.0,126.8,126.3,123.2,123.1, 121.4,113.7,93.2,56.0,35.2,30.9,30.8,22.5,21.6,14.0；
HRMS(ESI,m/z):calcd.for C35H35N2O3S+(M+H)+:requires 563.2362,found: 563.2365.
Embodiment 6
In the dry pressure-resistant reaction tubes of 15mL, 96mg 4- (3- fluorophenyls)-N- tolysulfonyl -1,2,3- tri- are added Nitrogen azoles, 44mg 3- (benzylidenei) indol-2-one, 9.9mg four [N- phthalyls-(S)-valine)] two rhodiums and 1.0mL 1,2- dichloroethanes.Under a nitrogen, 95 DEG C of stirring reactions 3 hours.Reaction end is cooled to room temperature, directly crosses silica gel (volume ratio of petroleum ether and ethyl acetate is 10 to post:1) product 42mg, is obtained, yield 41%, course of reaction is shown below：
The product that the present embodiment is prepared carries out nuclear magnetic resonance and mass spectral analysis：
1H NMR(600MHz,CDCl3):δ=10.13 (s, 1H), 7.82 (d, J=7.2Hz, 2H), 7.59 (d, J= 8.4Hz, 1H), 7.48 (t, J=7.8Hz, 1H), 7.25-7.27 (m, 2H), 7.02-7.09 (m, 4H), 6.92 (d, J= 7.2Hz,2H),6.83-6.87(m,1H),6.61-6.69(m,3H),4.97(s,1H),3.42(s,br,1H),2.39(s, 3H)；
13C NMR(150MHz,CDCl3):δ=173.3,145.9,145.6,144.1,136.9,136.1,132.7, 129.7,129.6,129.1,128.8,128.7,127.8,127.2,123.2,123.1,122.0,121.6,114.3, 114.2,113.9,113.8,113.6,92.7,56.0,21.6；
HRMS(ESI,m/z):calcd.for C30H24FN2O3S+(M+H)+:requires 511.1486,found: 511.1484.
Embodiment 7
In the dry pressure-resistant reaction tubes of 15mL, 99mg 4- (2- methoxyl groups) phenyl-N- tolysulfonyl -1,2 is added, 3- triazoles, 44mg 3- (benzylidenei) indol-2-one, 9.9mg four [N- phthalyls-(S)-valine)] two rhodiums and 1.0mL 1,2- dichloroethanes.Under a nitrogen, 95 DEG C of stirring reactions 3 hours.Reaction end is cooled to room temperature, directly crosses silica gel (volume ratio of petroleum ether and ethyl acetate is 9 to post:1) product 38mg, is obtained, yield 37%, course of reaction is shown below：
The product that the present embodiment is prepared carries out nuclear magnetic resonance and mass spectral analysis：
1H NMR(600MHz,CDCl3):δ=10.11 (s, 1H), 7.83 (d, J=7.8Hz, 2H), 7.57 (d, J= 8.4Hz, 1H), 7.46 (t, J=7.2Hz, 1H), 7.26 (d, J=6.0Hz, 2H), 7.23 (d, J=8.4Hz, 1H), 7.02- 7.07 (m, 4H), 6.91 (d, J=6.6Hz, 1H), 6.81 (t, J=7.2Hz, 1H), 6.49 (m, 2H), 6.45 (d, J= 7.8Hz,1H),4.95(s,1H),3.49(s,3H),3.41(s,br,1H),2.39(s,3H)；
13C NMR(150MHz,CDCl3):δ=174.0,158.7,145.8,145.4,143.9,143.7,137.1, 136.5,132.8,129.6,129.5,129.3,127.7,127.1,127.0,123.2,123.1,121.5,118.9, 113.8,113.5,112.3,93.1,56.0,55.1,21.6；
HRMS(ESI,m/z):calcd.for C31H27N2O4S+(M+H)+:requires 523.1686,found: 523.1690.
Embodiment 8
In the dry pressure-resistant reaction tubes of 15mL, 92mg 4- (2- thienyls)-N- tolysulfonyl -1,2,3- tri- are added Nitrogen azoles, 44mg 3- (benzylidenei) indol-2-one, 9.9mg four [N- phthalyls-(S)-valine)] two rhodiums and 1.0mL 1,2- dichloroethanes.Under a nitrogen, 95 DEG C of stirring reactions 3 hours.Reaction end is cooled to room temperature, directly crosses silica gel (volume ratio of petroleum ether and ethyl acetate is 10 to post:1) product 40mg, is obtained, yield 40%, course of reaction is shown below：
The product that the present embodiment is prepared carries out nuclear magnetic resonance and mass spectral analysis：
1H NMR(600MHz,CDCl3):δ=10.1 (s, 1H), 7.85 (d, J=7.8Hz, 2H), 7.57 (d, J= 8.4Hz, 1H), 7.45 (t, J=7.2Hz, 1H), 7.28 (d, J=7.8Hz, 2H), 7.16 (d, J=6.6Hz, 1H), 7.12 (t, J=7.2Hz, 2H), 7.07 (t, J=7.2Hz, 1H), 7.03 (d, J=7.2Hz, 2H), 6.88 (d, J=4.2Hz, 1H), 6.57 (s,1H),6.47(s,1H),5.00(s,1H),3.71(s,1H),2.41(s,3H)；
13C NMR(150MHz,CDCl3):δ=172.1,146.6,145.4,144.8,144.1,137.0,136.1, 131.9,129.6,129.5,129.2,127.8,127.3,127.2,125.8,125.2,125.1,123.3,123.1, 121.6,113.8,91.7,55.8,21.6；
HRMS(ESI,m/z):calcd.for C28H23N2O3S2 +(M+H)+:requires 499.1144,found: 499.1150.
Embodiment 9
In the dry pressure-resistant reaction tubes of 15mL, 84mg 4- butyl-N- tolysulfonyl -1,2 is added, 3- triazoles, The 1 of 44mg 3- (benzylidenei) indol-2-one, 9.9mg four [N- phthalyls-(S)-valine)] two rhodiums and 1.0mL, 2- dichloroethanes.Under a nitrogen, 95 DEG C of stirring reactions 3 hours.Reaction end is cooled to room temperature, directly crosses silicagel column (petroleum ether Volume ratio with ethyl acetate is 12:1) product 40mg, is obtained, yield 43%, course of reaction is shown below：
The product that the present embodiment is prepared carries out nuclear magnetic resonance and mass spectral analysis：
1H NMR(600MHz,CDCl3):δ=9.99 (s, 1H), 7.91 (d, J=7.8Hz, 2H), 7.54 (d, J= 8.4Hz, 1H), 7.45 (t, J=7.8Hz, 1H), 7.31-7.40 (m, 8H), 7.10 (t, J=7.8Hz, 1H), 4.71 (s, 1H), 3.41 (s, br, 1H), 2.43 (s, 3H), 1.33-1.41 (m, 2H), 0.76-0.92 (m, 4H), 0.49 (t, J=6.0Hz, 3H)；
13C NMR(150MHz,CDCl3):δ=174.4,145.1,144.4,144.0,143.9,137.5,136.5, 131.7,129.7,129.4,129.0,128.3,127.5,127.1,123.3,122.9,121.3,113.7,89.9,53.8, 39.1,25.0,22.7,21.6,13.5；
HRMS(ESI,m/z):calcd.for C28H29N2O3S+(M+H)+:requires 473.1893,found: 473.1889.
Embodiment 10
In the dry pressure-resistant reaction tubes of 15mL, 111mg 4- (4- amyl groups phenyl)-N- tolysulfonyl -1,2 is added, 3- triazoles, 60mg 3- (4- bromobenzyls methylene) indol-2-one, 9.9mg four [N- phthalyls-(S)-valine)] two The 1,2- dichloroethanes of rhodium and 1.0mL.Under a nitrogen, 95 DEG C of stirring reactions 3 hours.Reaction end is cooled to room temperature, direct mistake (volume ratio of petroleum ether and ethyl acetate is 10 to silicagel column:1) product 57mg, yield 45%, course of reaction such as following formula institute, are obtained Show：
The product that the present embodiment is prepared carries out nuclear magnetic resonance and mass spectral analysis：
1H NMR(600MHz,CDCl3):δ=10.12 (s, 1H), 7.83 (d, J=7.8Hz, 2H), 7.57 (d, J= 8.4Hz, 1H), 7.46 (t, J=7.8Hz, 1H), 7.26 (d, J=6.6Hz, 2H), 7.18 (d, J=8.4Hz, 1H), 7.13 (d, J=7.8Hz, 2H), 7.06 (t, J=7.8Hz, 1H), 6.71-6.78 (m, 6H), 4.88 (s, 1H), 3.33 (s, br, 1H), 2.39 (s, 3H), 2.37 (t, J=7.2Hz, 2H), 1.39-1.42 (m, 2H), 1.24-1.28 (m, 2H), 1.10-1.14 (m, 2H), 0.84-0.89 (t, J=7.2Hz, 3H)；
13C NMR(150MHz,CDCl3):δ=174.1,145.3,144.8,143.9,142.4,139.2,137.1, 135.8,132.9,130.9,130.7,129.6,129.5,127.6,127.1,126.2,122.9,121.6,120.9, 113.9,93.1,55.3,35.2,31.0,30.9,22.5,21.6,14.0；
HRMS(ESI,m/z):calcd.for C35H34BrN2O3S+(M+H)+:requires 641.1468,found: 641.1467.
Embodiment 11
In the dry pressure-resistant reaction tubes of 15mL, 111mg 4- (4- amyl groups phenyl)-N- tolysulfonyl -1,2 is added, 3- triazoles, 50mg 3- (benzylidenei) -5- methoxy-Indole -2- ketone, 9.9mg four [N- phthalyls-(S)-figured silk fabrics ammonia Acid)] two rhodiums and 1.0mL 1,2- dichloroethanes.Under a nitrogen, 95 DEG C of stirring reactions 3 hours.Reaction end is cooled to room temperature, Directly crossing silicagel column, (volume ratio of petroleum ether and ethyl acetate is 10:1) product 64mg, is obtained, yield 54%, course of reaction is such as Shown in following formula：
The product that the present embodiment is prepared carries out nuclear magnetic resonance and mass spectral analysis：
1H NMR(600MHz,CDCl3):δ=10.11 (s, 1H), 7.83 (d, J=7.2Hz, 2H), 7.56 (d, J= 8.4Hz, 1H), 7.44 (t, J=7.2Hz, 1H), 7.24-7.26 (m, 3H), 7.05 (t, J=7.2Hz, 1H), 6.93 (t, J= 7.8Hz, 1H), 6.81 (d, J=7.8Hz, 2H), 6.71 (d, J=7.8Hz, 2H), 6.60 (d, J=7.8Hz, 1H), 6.53 (d, J=7.2Hz, 1H), 6.33 (s, 1H), 4.90 (s, 1H), 3.51 (s, 3H), 3.29 (s, br, 1H), 2.38 (s, 3H), 2.36 (t, J=7.2Hz, 2H), 1.37-1.39 (m, 2H), 1.22-1.25 (m, 2H), 1.10-1.12 (m, 2H), 0.83-0.86 (t, J =7.2Hz, 3H)；
13C NMR(150MHz,CDCl3):δ=174.5,159.1,145.7,145.4,143.9,142.1,139.5, 137.2,132.8,129.5,129.4,128.6,127.3,127.1,126.4,123.2,123.1,122.0,121.4, 114.4,113.8,113.1,93.2,56.0,55.1,35.2,31.0,30.9,22.5,21.6,14.0；
HRMS(ESI,m/z):calcd.for C36H37N2O4S+(M+H)+:requires 593.2468,found: 593.2464。

Claims (10)

  1. A kind of 1. method for preparing Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative, it is characterised in that in organic solvent, rhodium catalysis Under agent catalysis, N- sulfonyls -1,2,3-triazoles class compound has following with 3- methylene indol-2-one derivatives one-step synthesis The 1,4- oxygen Azepinoindole analog derivatives of structure shown in chemical formula (I)：
    Described N- sulfonyl -1,2,3- triazole class compounds have the structure shown in chemical formula (II)：
    Described 3- methylene indol-2-one derivatives have the structure shown in chemical formula (III)：
    In chemical formula (I)~(III), R1The alkyl for being 1~12 for carbon number, aryl, substituted aryl, heteroaryl；R2For virtue Base, substituted aryl or carbon number are 1~6 alkyl；R3It is 1~6 for aryl, substituted aryl, heteroaryl or carbon number Alkyl；R4The alkyl for being 1~6 for H, carbon number, halogen atom, methoxyl group；Wherein, R1、R2And R3In aryl on substituent Independently selected from halogen, CF3、CN、C1~C5Alkyl, C1~C4Alkanoyl or C1~C4Alkoxy.
  2. 2. the method as claimed in claim 1 for preparing Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative, it is characterised in that described Aryl is phenyl or naphthyl；Described heteroaryl is thienyl or furyl.
  3. 3. the method as claimed in claim 1 for preparing Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative, it is characterised in that R1And R3 In aryl on substituent independently selected from F, CF3, formoxyl, amyl group, methoxyl group.
  4. 4. the method as claimed in claim 1 for preparing Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative, it is characterised in that R4For H, Methoxyl group.
  5. 5. the method as claimed in claim 1 for preparing Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative, it is characterised in that described N- sulfonyls -1,2,3-triazoles class compound and the mol ratio of described 3- methylene indol-2-one derivatives are 1:1~4:1.
  6. 6. the method as claimed in claim 1 for preparing Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative, it is characterised in that described The mol ratio of rhodium catalyst and described N- sulfonyl -1,2,3- triazole class compounds is 0.005~0.04:1.
  7. 7. the method as claimed in claim 1 for preparing Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative, it is characterised in that reaction temperature Spend for 80~140 DEG C；Reaction time is 1~6h.
  8. 8. the method as claimed in claim 1 for preparing Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative, it is characterised in that described Rhodium catalyst is the rhodium of tetraacethyl two, four sad two rhodiums or the rhodium of four pivalic acid two, four [N- phthalyls-(S)-valine)] two One or more in rhodium.
  9. 9. the method as claimed in claim 1 for preparing Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative, it is characterised in that described Organic solvent is the one or more in dichloromethane, chloroform, toluene, ethyl acetate, 1,2- dichloroethanes.
  10. 10. the method as claimed in claim 1 for preparing Isosorbide-5-Nitrae-oxygen Azepinoindole analog derivative, it is characterised in that reaction Temperature is 90~100 DEG C, and catalyst is four [N- phthalyls-(S)-valine)] two rhodiums.
CN201710839849.1A 2017-09-18 2017-09-18 A kind of method for preparing 1,4 oxygen Azepinoindole analog derivatives Pending CN107868093A (en)

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Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
JESSICA RAUSHEL ET AL.: "Efficient Synthesis of 1-Sulfonyl-1,2,3-triazoles", 《ORG. LETT.》 *
TOMOYA MIURA ET AL.: "Stereoselective Synthesis of 2,3-Dihydropyrroles from Terminal Alkynes,Azides,and α,β-Unsaturated Aldehydes via N-Sulfonyl-1,2,3-triazoles", 《J.AM.CHEM.SOC.》 *
TOMOYA MIURA ET AL.: "Synthesis of α-Amino Ketones from Terminal Alkynes via Rhodium-Catalyzed Denitrogenative Hydration of N-Sulfonyl-1,2,3-triazoles", 《J. AM. CHEM.SOC.》 *

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