CN112028813B - 4-chloro indole compound and preparation method thereof - Google Patents
4-chloro indole compound and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a 4-chloro indole compound and a preparation method thereof. Various N-protected indole-3-formaldehydes and N-chlorosuccinimide (NCS) are used as reaction substrates to prepare 4-chloro indole compounds. The reaction yield can reach medium to excellent, the chemical selectivity and the regioselectivity of the reaction are excellent, the reaction condition is mild, and the application range of the substrate is wide; the method has the advantages of simple and convenient operation, low cost, less side reaction, high product purity, convenient separation and purification and suitability for large-scale preparation, so the obtained product has good application prospect in the field of biological medicine.
Description
Technical Field
The invention relates to a heterocyclic compound and a preparation method thereof, in particular to a 4-site chloroindole compound and a preparation method thereof.
Background
The nitrogen-containing heterocyclic compound is a common core structure of natural products and a plurality of drug molecules, and the indole has a special structure of the benzopyrrole and is an important natural nitrogen-containing alkaloid compound. Indole Heterocyclic compounds tend to have a broad spectrum of physiological and pharmacological activities in most cases, so that rapid and efficient synthesis of indole compounds and their diversity modification have attracted research interest from a wide range of organic and pharmaceutical chemists ((a) N.K.Kaushik, N.Kaushik, P.Attri, N.Kumar, C.H.Kim, A.K.Verma, E.H.Choi, Molecules,2013,18, 6620-. In fact, Fisher et al developed a well-known Fisher indole synthesis reaction (E.Fischer, F.Jourdan, Ber.Dtsch.Chem.Ges.1883,16,2241) as early as 1883, and chemists reported improved indole synthesis methods ((a) T.Guo, F.Huang, L.Yu, Z.Yu, Tetrahedron Lett.2015,56, 296-302), (b) M.Inman, C.J.Moody, Chem.Sci.2013,4,29-41, (c) N.Yoshikai, Y.Wei, Asian J.Org.Chem.2013, Shid-2,466 d), Z.2012, F.Glorius, Angew.Chem.Ed.Ed.51, 9220, M.283, Amarh.2011.J.Chevrol, Shi.68, Dec.J.73, Rockwell-19, Rockwell-32, Rab.R.J.Motif.Motif.70, Shi.51, Rock.22, Shi.12, Rock.12, Rockwell-32, Tex.11, Shi.70, Shi.12, Shi.32, Shi.R.7, Shi.12, Shi.III, Shi.V, Shi.III, Shi.R.R.R.R.7, Shi.7, Shi, Shi.7, Shi.R.R.R.R.R.R.R.R.7, Kr.7, Shi.7, Kraft, Shi.III, Shi.R.R.7, Shi.R.7, III, Shi.R.7, III, Shi.R.R.7, Taber, III, Taber, III, Taber, III, Taber, R.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P.P. The research in two decades recently found that the transition metal can effectively catalyze the direct function of inert carbon-hydrogen Bond, and has the advantages of no need of pre-Activation of substrate, good selectivity, high efficiency, etc., which is a new research hotspot in the field of organic Chemistry ((a) J.Q.Yu, Z.J.Shi (Eds.), C-H Activation, Topics in Current Chemistry, Springer, Heidelberg, Germany, 2010), (b) P.H.Dixneuf, H.Doucet (Eds.), C-H Activation and catalysis function, Chemics in Current Chemistry, Springer, Heidelberg, German, 2016, (C) H.M.L.Davies, D.Morton, J.org.Chem.2016,81,343, 350 d, T.H.H.J.Org.M.2016, 81, 350, K.H.K., K.H.H.H.H.J.H.H.J.H.D.Morton, J.H.H.S.H.H.H.H.H.H.H.H.H.H.H.H.D.H.H.H.H.H.M.H.D.D.H.S., Morton, J.S., Ser. No. H.H.H.H.H.H.H.H.H.H.H.H.H.H.H.H.H.H.H.H.S. (No. H.S. (No. H.H.H.H.S. H.S. (No. H.S., (R.S. H.S., (R.S. H.S. H.S.,. H.S. (No. H.S. H.H.S., (R.S.,. H.S.,. H.H.H.S. H.S. (No. H.S., (R.S.,. H.H.S., (R.S., (R.) (R. In particular, the temporary directing group strategy appeared in the last three years is used for transition metal catalyzed direct hydrocarbon functionalization, the introduction and elimination of the covalent bond of the traditional directing group can be avoided by in situ reversible generation of imine and the temporary directing group is released by hydrolysis, the atom economy and the step economy of hydrocarbon activation are greatly improved, and the practical application of hydrocarbon activation in organic Synthesis and pharmaceutical chemistry is greatly enhanced ((a) Q.ZHao, T.Poisson, X.Pannecuche, T.Besset, Synthesis 2017,49, 4808-Stroan, L.Ackermann, chem.2018,4, 199-222; (c) S.St-Campbell, J.A.Bufonic, Org.Biomol.chem.2018,16, 4582-4595; (d) O.K.Rashyd, B.Cherng, ChemestrySet, J.A.2013, RSC.201arhaar.89, RSC.578, Aust K.56, Aust K.K.K.K.K.Hashimoto.1948, Aust.56, Aust.8, Pic.48, Aust.K.K.K.K.K.K. Lab.K. K. 35, S. K. Chen, S. K. Chen, Chem, S. K. Chen, S. K. Chen, B.K. K. Chen, S. K. Chen, S. K. Chen, B.K. K. Chen, B.K. Chen.K. Chen, B.K. K. Chen, S. K.. The efficient synthesis of indole compounds by rhodium catalysis from acetanilide compounds and internal alkynes was reported by the Fagnou group in 2008 and 2010, respectively, as starting materials ((a) D.R. Stuart, M.Bertrand-Laperle, K.M.N.Burgess, K.Fagnou, J.Am.chem.Soc.2008,130,16474-16475, (b) D.R. Stuart, P.Alsabeh, M.Kuhn, K.Fagnou, J.Am.chem.Soc.2010,132, 18326-18339). We have been interested in the synthesis of nitrogen-containing heterocyclic compounds and their pharmaceutical activity studies, and recently we have reported that copper-catalyzed o-bromobenzaldehyde and glycine ester hydrochloride one-pot synthesis of 2-carboxylate substituted indole compounds gives moderate to excellent yields under mild reaction conditions (z.zhu, j.yuan, y.zhou, q.yang, j.xu, y.peng, eur.j.org.chem.2014, 511-514). And starting from acetanilide and trifluoromethyl substituted phenylacetylene, the 3-trifluoromethyl substituted indole compound (Y.Zhou, C.Zhang, J.Yuan, Q.Yang, Q.Xiao, Y.Peng, Tetrahedron Lett.2016,57, 3222-substituted 3225) is efficiently prepared by rhodium catalyzed one-step hydrocarbon activated oxidative cyclization.
The halogenated indole compound is a special indole compound, and the structural characteristics of the halogenated indole compound mean that one or more hydrogen atoms on an indole parent ring are replaced by halogen atoms. Among them, the 4-position chloroindole compound tends to have excellent pharmaceutical and physiological activities, such as: 4-chloro radicalThe indole-substituting compound D512 can be used for treating Parkinson's disease (B.das, S.Vedachalam, D.Luo, T.Antonio, M.E.A.Reith, A.K.Dutta, J.Med.chem.2015,58, 9179-9195); the 4, 6-dichloroindole compound NEU-1053 can be used for treating human African trypanosomiasis (W.G.Devine, R.Diaz-Gonzalez, G.Ceballos-Perez, D.Rojas, T.Satoh, W.tear, R.M.Ranade, X.Barros
W.G.J.Hol, F.S.Buckner, M.Navarro, M.P.Pollastri, ACS infection.Dis.2017, 3, 225-; the 4, 6-dichloroindole carboxylic acid derivative PSB-12150 as an effective antagonist of GPR17 ligand may be a potential new drug precursor (M) for multiple sclerosis, brain and cerebrospinal injuries and neurodegenerative diseases.
K.Ritter, K.Thiemeke, M.Gillard, E.Kostenis, C.E.Muller, ACS Med.Chem.Lett.2014,5, 326-; MDL-29951 can act as an allosteric inhibitor of fructose-1, 6-bisphosphatase (s.w.wright, a.a.carlo, d.e.danley, d.l.hageman, g.a.karam, m.n.mansour, l.d.mcclure, j.pandit, g.k.schulte, j.l.treadway, i.wang, p.h.bauer, bioorg.med.chem.len.2003, 132055-2058); GV150526, as a potent glycine binding site antagonist, is effective in protecting the nervous system of post-stroke brain injury ((a) R.D.Fabio, N.Conti, E.D.Magistris, A.Feriani, S.Provera, F.M.Sabbatini, A.Reggiani, L.Rovatti, R.J.Barnaby, J.Med.chem.1999,42, 3486-.
G.dannhardt, j.med.chem.2003,46, 64-73; (c) baron, r.j.cresge, r.a.farr, d.friedrich, r.s.gross, b.l.harrison, d.a.janowick, d.matthews, t.c.mccloskey, s.meikrantz, p.l.nyce, r.vaz, w.a.metz, j.med.chem.2005,48, 995-; 4, 6-dichloroindoleamide derivatives are useful as potential antituberculosis drugs (R.R.Kondreddi, J.Jircick, S.P.S.Rao, S.B.Lakshminarayana, L.R.Camacho, R.Rao, M.Herve, P.Bifani, N.L.Ma, K.Kuhen, A.Goh, A.K.chatterjee, T.Dick, T.T.Diagana, U.H.Manjuntha, P.W.Smith, J.Med.Chem.2013,56,8849- -8859) and as antituberculosis drugsMycobacterial infectives (a.p.kozikowski, o.k.onajole, j.stec, c.dupont, a.viljoen, m.richard, t.chaira, s.lun, w.bishai, s.raj, d.ordway, l.kremer, j.med.chem.2017,60, 5876-. On the other hand, the 4-position halogenated indole compound plays a great role in the research of the total synthesis of natural products as an important synthetic building block, and is used by many organic chemists for the total synthesis research of a series of complex nitrogen-containing natural products, such as: shanghai organic institute, a large panel of Okinawa, used in the total synthesis of natural products Communnins A and B (Z.Zuo, D.Ma, Angew. chem. int. Ed.2011,50, 12008-12011); the japanese Itami group used in the total synthesis of the natural product Dragmacidin D (d.mandal, a.d.yamaguchi, j.yamaguchi, k.itami, j.am.chem.soc.2011,133, 19660-19663); the German Opatz group was used in the total synthesis of the natural product Cyclocelavire (N.Netz, T.Opatz, J.org.Chem.2016,81, 1723-1730); professor Aggarwal, university of bristol, england, recently used it in the total synthesis of the natural product Cyclopiazonic Acid (o.zhurakovskyi, y.e.tgrkmen, l.e).
V.a. moorthie, c.c. chen, m.a. shaw, m.r.crimmin, m.ferrara, m.ahmad, m.ostovar, j.v. matlock, v.k.aggarwal, angelw.chem.int.ed.2018, 57, 1346-; ohno and Fukuyama et al, Japan, were independently used for the total synthesis of the natural product Lysergic Acid ((a) S.Inuki, S.Oishi, N.Fujii, H.Ohno, org.Lett.2008,10, 5239-shot 5242; (b) A.Iwata, S.Inuki, S.Oishi, N.Fujii, H.Ohno, J.Org.Chem.2011,76, 5506-shot 5512; (c) S.Umezaki, S.Yokoshima, T.Fukuyama; org.Lett.2013,15, 4230-shot 4233), respectively.
Therefore, the method for researching and developing the 4-site halogenated indole compound has important scientific theory research significance and practical application value by selectively introducing the halogen region into the indole skeleton. However, through extensive literature research we have found that the methods reported in the literature for synthesizing such compounds are quite limited, and there are currently only three known methods for preparing halogenated indoles in the 4-position. The first uses thallium trifluoroacetate (Tl) to halogenate the indole 4 position in trifluoroacetic acid ((a) S.E.Adams, C.Parr, D.J.Miller, R.K.Allemann, M.B.Hallett, Med.Chem.Commun.2012,3,566-. The second method employs mercury acetate (Hg) to halogenate indole at the 4-position in acetic acid (M.A. Brown, M.A. Kerr, Tetrahedron Lett.2001,42, 983-. The third method uses tert-butyl lithium, a superbase, to halogenate indole 4-position at low temperature in ether (B.Chauder, A.Larkin, V.Snieckus, org.Lett.2002,4, 815-817). As is known, thallium (Tl) and mercury (Hg) are toxic heavy metals, and tert-butyl lithium is very active and reacts violently with air to cause fire or even explosion once the operation is not proper, so that the three known methods reported in the documents have insurmountable defects and limitations, and are difficult to apply on a large scale in actual production.
Disclosure of Invention
In view of the above problems, an object of the present invention is to provide a 4-chloroindole compound and a method for preparing the same.
In one aspect of the present invention, there is provided a 4-chloroindole compound represented by formula 3:
wherein R is selected from hydrogen and C1～C8Alkyl radical, C1～C8Alkoxy, halogen; PG represents a protective group selected from the group consisting of benzoyl, p-toluyl, p-methoxybenzyl, p-tert-butylbenzoyl, p-phenylbenzoyl, p-fluorobenzyl, p-chlorobenzyl, p-trifluoromethylbenzoyl, m-toluyl, m-chlorobenzyl, 1-naphthoyl, 2-naphthoyl, acetyl, benzyloxycarbonyl (Cbz), p-toluenesulfonyl, methanesulfonyl, p-nitrobenzenesulfonyl, furoyl and thenoyl.
Preferably, R is selected from hydrogen, methyl, ethyl, n-propyl, methoxy, ethoxy, fluoro, chloro, bromo; PG is selected from benzoyl, p-toluoyl, p-methoxybenzoyl, p-tert-butylbenzoyl, p-phenylbenzoyl, p-fluorobenzoyl, p-chlorobenzoyl, p-trifluoromethylbenzoyl, m-toluoyl, m-chlorobenzoyl, 1-naphthoyl, 2-naphthoyl, acetyl, carbobenzoxy (Cbz), p-toluenesulfonyl, methanesulfonyl, p-nitrobenzenesulfonyl, furoyl, thenoyl.
More preferably, the 4-chloroindole compound represented by formula 3 is specifically one of the following compounds:
n-benzoyl-4-chloroindole-3-carbaldehyde;
n-acetyl-4-chloroindole-3-carbaldehyde;
n-benzyloxycarbonyl-4-chloroindole-3-carbaldehyde;
n-p-toluenesulfonyl-4-chloroindole-3-carbaldehyde;
n-methanesulfonyl-4-chloroindole-3-carbaldehyde;
n-p-nitrobenzenesulfonyl-4-chloroindole-3-carbaldehyde;
n- (furan-2-carbonyl) -4-chloroindole-3-carbaldehyde;
n- (thiophene-2-formyl) -4-chloroindole-3-carbaldehyde;
n-p-toluoyl-4-chloroindole-3-carbaldehyde;
n-p-methoxybenzoyl-4-chloroindole-3-carbaldehyde;
n-p-tert-butylbenzoyl-4-chloroindole-3-carbaldehyde;
n-p-phenylbenzoyl-4-chloroindole-3-carbaldehyde;
n-p-fluorobenzoyl-4-chloroindole-3-carbaldehyde;
n-p-chlorobenzoyl-4-chloroindole-3-carbaldehyde;
n-p-trifluoromethylbenzoyl-4-chloroindole-3-carbaldehyde;
n-m-toluoyl-4-chloroindole-3-carbaldehyde;
n-m-chlorobenzoyl-4-chloroindole-3-carbaldehyde;
n- (1-naphthoyl) -4-chloroindole-3-carbaldehyde;
n- (2-naphthoyl) -4-chloroindole-3-carbaldehyde;
n-benzoyl-4-chloro-5-fluoroindole-3-carbaldehyde;
n-benzoyl-4-chloro-5-fluoroindole-3-carbaldehyde;
n-benzoyl-4-chloro-5-fluoroindole-3-carbaldehyde;
n-benzoyl-4-chloro-6-methylindole-3-carbaldehyde;
n-benzoyl-4-chloro-6-methoxyindole-3-carbaldehyde;
n-benzoyl-4, 6-dichloroindole-3-carbaldehyde;
n-benzoyl-4-chloro-7-methylindole-3-carbaldehyde.
In another aspect, the present invention provides a method for preparing the 4-chloroindole compound, which comprises the following steps:
reacting the compound shown in the formula 1 with N-chlorosuccinimide (NCS) in an organic solvent under the participation of a guide group, an acid additive and a catalyst to obtain the 4-chloro indole compound; the reaction formula is as follows:
wherein R is selected from hydrogen and C1～C8Alkyl radical, C1～C8Alkoxy, halogen; PG is selected from benzoyl, p-toluoyl, p-methoxybenzoyl, p-tert-butylbenzoyl, p-phenylbenzoyl, p-fluorobenzoyl, p-chlorobenzoyl, p-trifluoromethylbenzoyl, m-toluoyl, m-chlorobenzoyl, 1-naphthoyl, 2-naphthoyl, acetyl, carbobenzoxy (Cbz), p-toluenesulfonyl, methanesulfonyl, p-nitrobenzenesulfonyl, furoyl, thenoyl.
In the above method, the molar ratio of the compound represented by formula 1 to N-chlorosuccinimide may be 1:1.2 or 1: 1.5.
In the above method, the organic solvent may be chlorobenzene or 1, 2-dichloroethane.
In the above process, the catalyst may be palladium acetate, palladium trifluoroacetate or palladium bis (dibenzylideneacetone).
In the above method, the directing group may be 2-aminobenzoic acid, 2-amino-4-nitrobenzoic acid, 2-amino-5-nitrobenzoic acid, 2-amino-6-nitrobenzoic acid, 2-amino-4-trifluoromethylbenzoic acid, 2-amino-4-chlorobenzoic acid, ethyl 2-aminobenzoate or 2-aminoacetophenone.
In the above method, the acid additive may be trifluoroacetic acid, perfluorobutyric acid or diphenylphosphoric acid.
In the above method, the reaction temperature may be 50 ℃ and the reaction time may be 24 hours.
In another aspect, the invention provides the use of the 4-chloro indole compound, and the 4-chloro indole compound can be applied to the field of biomedicine, for example, used as a raw material for preparing medicaments for treating Parkinson's disease, humanized African trypanosomiasis medicaments, multiple sclerosis medicaments, medicaments for treating brain and cerebrospinal injuries and neurodegenerative diseases, fructose-1, 6-bisphosphatase allosteric inhibitors, glycine binding site antagonists, antituberculosis medicaments and medicaments for resisting mycobacterium abscessus infection.
The invention has the technical effects that: various N-protected indole-3-formaldehydes are adopted as reaction substrates, and are subjected to direct carbon hydrogen activated chlorination reaction with N-chlorosuccinimide (NCS) under the catalysis of palladium acetate by the aid of a temporary guide group to prepare a 4-site chloroindole compound. The method has the advantages of moderate to excellent reaction yield, excellent chemical selectivity and regioselectivity of the reaction, mild conditions, wide substrate application range, simple and convenient operation, low cost, less side reaction, high product purity, convenient separation and purification and suitability for large-scale preparation. The product obtained by the method has potential biological and pharmaceutical activities, so the method can be applied to the field of biological medicines and has a very good application prospect.
Drawings
FIG. 1 is a diagram showing the X-single crystal diffraction pattern of N-benzoyl-4-chloroindole-3-carbaldehyde compound 3 a.
FIG. 2 is a molecular structure diagram of a compound corresponding to a single crystal structure of N-benzoyl-4-chloroindole-3-carbaldehyde compound 3 a.
Detailed Description
The following detailed description will be provided with the advantages of the present invention in conjunction with the embodiments of the drawings, which are intended to help the reader to better understand the spirit of the present invention, but not to limit the scope of the present invention.
The method of the invention can be specifically operated as follows: adding various N-protected indole-3-formaldehyde or derivatives thereof (compounds shown in formula 1), N-chlorosuccinimide (NCS), palladium acetate serving as a catalyst, 2-amino-4-nitrobenzoic acid serving as a temporary guide group and trifluoroacetic acid serving as an acid additive into a reaction test tube in sequence, adding chlorobenzene serving as a solvent, and sealing the reaction test tube by using a rubber plug; placing the test tube in an oil bath at 50 ℃, stirring and heating for about 24 hours, and detecting by TLC in the reaction process until complete reaction; the solvent is firstly dried by spinning during the post-treatment, and the pure product 4-chloro indole (the compound shown in the formula 3) is obtained by directly separating through silica gel column chromatography.
Example 1
N-benzoylindole-3-carbaldehyde (0.2mmol), N-chlorosuccinimide (0.24mmol), palladium acetate (10 mol%) as a catalyst, 2-amino-4-nitrobenzoic acid (45 mol%) as a temporary directing group, trifluoroacetic acid (10.0equiv) as an acid additive were added to a reaction tube in this order, and finally chlorobenzene (1mL) as a solvent was added, and the reaction tube was sealed with a rubber stopper. The test tube is placed in an oil bath at 50 ℃ and heated for about 24 hours with stirring, and TLC is used for detecting the reaction until the reaction is completed in the reaction process. The solvent is firstly dried by spinning during the post-treatment, and the pure product N-benzoyl-4-chloroindole-3-formaldehyde compound 3a is obtained by directly separating on silica gel column chromatography.
examples 2 to 24 were obtained in substantially the same manner as in example 1, with only the corresponding reactants changed.
Example 2
The reactants are N-acetyl indole-3-formaldehyde and N-chlorosuccinimide, and the product is N-acetyl-4-chloroindole-3-formaldehyde compound 3 b.
N-acetyl-4-chloroindole-3-formaldehyde compound 3b, the yield is 80 percent; a white solid; melting point 170-;1H NMR(400MHz,CDCl3)δ10.79(s,1H),8.43(d,J＝8.0Hz,1H),8.21(s,1H),7.39(d,J＝8.0Hz,1H),7.33(t,J＝8.0Hz,1H),2.73(s,3H)；13C NMR(100MHz,CDCl3)δ187.1,168.9,137.4,130.5,126.7,126.0,125.9,125.0,122.2,115.6,23.8；HRMS(pos.ESI):m/z[M+H]+for C11H9ClNO2calcd:222.0316,found:222.0351。
example 3
The reactants are N-carbobenzoxy indole-3-formaldehyde and N-chlorosuccinimide, and the product is N-carbobenzoxy-4-chloroindole-3-formaldehyde compound 3 c.
N-carbobenzoxy-4-chloroindole-3-formaldehyde compound 3c, wherein the yield is 46 percent; a white solid; the melting point is 93-95 ℃;1H NMR(400MHz,CDCl3)δ10.78(s,1H),8.42(s,1H),8.23(d,J＝8.0Hz,1H),7.50–7.43(m,5H),7.39(d,J＝8.0Hz,1H),7.33(t,J＝8.0Hz,1H),5.49(s,2H)；13C NMR(100MHz,CDCl3)δ186.9,149.8,137.2,134.0,131.2,129.3,129.0,128.9,126.3,126.2,125.4,125.1,121.8,114.3,70.1；HRMS(pos.ESI):m/z[M+H]+for C17H13ClNO3 calcd:314.0578,found:314.0624。
example 4
The reactants are N-p-toluenesulfonyl indole-3-formaldehyde and N-chlorosuccinimide, and the product is N-p-toluenesulfonyl-4-chloroindole-3-formaldehyde compound 3 d.
N-p-toluenesulfonyl-4-chloroindole-3-formaldehyde compound 3d, wherein the yield is 83 percent; a white solid; melting point 157-;1H NMR(400MHz,CDCl3)δ10.73(s,1H),8.40(s,1H),7.94(d,J＝8.0Hz,1H),7.84(d,J＝8.0Hz,2H),7.37–7.29(m,4H),2.38(s,3H)；13C NMR(100MHz,CDCl3)δ186.4,146.5,136.1,134.1,131.8,130.4,127.4,126.6,126.0,125.5,125.3,121.9,112.4,21.7；HRMS(pos.ESI):m/z[M+H]+for C16H13ClNO3S calcd:334.0299,found:334.0324。
example 5
The reactants are N-methylsulfonyl indole-3-formaldehyde and N-chlorosuccinimide, and the product is N-methylsulfonyl-4-chloroindole-3-formaldehyde compound 3 e.
The yield of the N-methylsulfonyl-4-chloroindole-3-formaldehyde compound 3e is 84 percent; a white solid; melting point 184-187 deg.C;1H NMR(400MHz,CDCl3)δ10.79(s,1H),8.28(s,1H),7.89(d,J＝8.4Hz,1H),7.46(d,J＝7.6Hz,1H),7.39(t,J＝8.0Hz,1H),3.29(s,3H)；13C NMR(100MHz,CDCl3)δ186.3,136.2,131.6,127.0,126.4,125.8,125.4,121.9,111.9,42.1；HRMS(pos.ESI):m/z[M+H]+for C10H9ClNO3S calcd:257.9986,found:257.9996。
example 6
The reactants are N-p-nitrobenzenesulfonylindole-3-formaldehyde and N-chlorosuccinimide, and the product is N-p-nitrobenzenesulfonyl-4-chloroindole-3-formaldehyde compound 3 f.
N-p-nitrobenzenesulfonyl-4-chloroindole-3-formaldehyde compound 3f with the yield of 83 percent; a white solid; melting point 193-;1H NMR(400MHz,DMSO-d6)δ10.51(s,1H),8.75(s,1H),8.49(d,J＝8.8Hz,2H),8.40(d,J＝8.8Hz,2H),8.04(d,J＝8.0Hz,1H),7.54–7.47(m,2H)；13C NMR(100MHz,DMSO-d6)δ185.8,151.8,141.2,136.1,134.7,129.8,127.6,126.5,126.4,125.8,125.0,122.6,112.9；HRMS(pos.ESI):m/z[M+H]+for C15H10ClN2O5S calcd:364.9993,found:364.9995。
example 7
The reactants are N- (furan-2-formyl) indole-3-formaldehyde and N-chlorosuccinimide, and the product is 3g of N- (furan-2-formyl) -4-chloroindole-3-formaldehyde compound.
3g of N- (furan-2-formyl) -4-chloroindole-3-formaldehyde compound, wherein the yield is 75%; a white solid; melting point 138-140 ℃;1H NMR(400MHz,CDCl3)δ10.83(s,1H),8.79(s,1H),8.39(d,J＝8.0Hz,1H),7.79(d,J＝0.8Hz,1H),7.55(d,J＝3.6Hz,1H),7.42(d,J＝8.0Hz,1H),7.35(t,J＝8.0Hz,1H),6.71(dd,J＝3.6,1.6Hz,1H)；13C NMR(100MHz,CDCl3)δ187.2,156.3,147.7,145.8,138.2,132.2,126.3,126.1,126.0,125.0,122.8,122.3,115.4,113.0；HRMS(pos.ESI):m/z[M+H]+for C14H9ClNO3calcd:274.0265,found:274.0276。
example 8
The reactants are N- (thiophene-2-formyl) indole-3-formaldehyde and N-chlorosuccinimide, and the product is N- (thiophene-2-formyl) -4-chloroindole-3-formaldehyde compound for 3 h.
N- (thiophene-2-formyl)The 4-chloroindole-3-formaldehyde compound is reacted for 3 hours, and the yield is 68 percent; a white solid; melting point 138-141 ℃;1H NMR(400MHz,CDCl3)δ10.83(s,1H),8.43(s,1H),8.29(d,J＝8.4Hz,1H),7.84(dd,J＝4.8,0.4Hz,1H),7.74(dd,J＝3.6,0.4Hz,1H),7.44(d,J＝7.6Hz,1H),7.37(t,J＝8.0Hz,1H),7.26(t,J＝4.4Hz,1H)；13C NMR(100MHz,CDCl3)δ187.0,161.4,137.9,135.4,135.0,134.9,132.3,128.4,126.3,126.2,126.0,125.3,121.8,114.9；HRMS(pos.ESI):m/z[M+H]+for C14H9ClNO2S calcd:290.0037,found:290.0062。
example 9
The reactants are N-p-toluoyl indole-3-formaldehyde and N-chlorosuccinimide, and the product is N-p-toluoyl-4-chloroindole-3-formaldehyde compound 3 i.
N-p-toluoyl-4-chloroindole-3-formaldehyde compound 3i, the yield is 69%; a yellow solid; melting point 158-;1H NMR(400MHz,CDCl3)δ10.78(s,1H),8.31(dd,J＝8.2,0.6Hz,1H),8.10(s,1H),7.65(d,J＝8.0Hz,2H),7.44(dd,J＝7.6,0.8Hz,1H),7.36(d,J＝8.0Hz,3H),2.48(s,3H)；13C NMR(100MHz,CDCl3)δ187.0,168.5,144.4,138.0,133.1,129.9,129.8,129.6,126.2,126.1,125.9,125.3,121.4,115.1,21.7；HRMS(pos.ESI):m/z[M+H]+for C17H13ClNO2calcd:298.0629,found:298.0625。
example 10
The reactants are N-p-methoxybenzoyl indole-3-formaldehyde and N-chlorosuccinimide, and the product is N-p-methoxybenzoyl-4-chloroindole-3-formaldehyde compound 3 j.
N-p-methoxybenzoyl-4-chloroindole-3-carbaldehyde compound 3j with a yield of 65%(ii) a A white solid; melting point 150-;1H NMR(400MHz,CDCl3)δ10.81(s,1H),8.27(d,J＝8.0Hz,1H),8.15(s,1H),7.76(d,J＝8.8Hz,2H),7.43(d,J＝7.6Hz,1H),7.36(t,J＝8.0Hz,1H),7.05(d,J＝8.8Hz,2H),3.93(s,3H)；13C NMR(100MHz,CDCl3)δ187.1,167.9,163.9,138.0,133.1,132.4,126.1,125.7,125.3,124.3,121.2,115.0,114.5,55.7；HRMS(pos.ESI):m/z[M+H]+for C17H13ClNO3calcd:314.0578,found:314.0600。
example 11
The reactants are N-p-tert-butylbenzoyl indole-3-formaldehyde and N-chlorosuccinimide, and the product is N-p-tert-butylbenzoyl-4-chloroindole-3-formaldehyde compound 3 k.
3k of N-p-tert-butylbenzoyl-4-chloroindole-3-formaldehyde compound, wherein the yield is 78%; a yellow solid; melting point 143-145 ℃;1H NMR(400MHz,CDCl3)δ10.80(s,1H),8.36(d,J＝8.0Hz,1H),8.13(s,1H),7.69(d,J＝8.4Hz,2H),7.58(d,J＝8.4Hz,2H),7.43(d,J＝8.0Hz,1H),7.37(t,J＝8.0Hz,1H),1.39(s,9H)；13C NMR(100MHz,CDCl3)δ187.1,168.6,157.4,138.0,133.2,129.7,129.6,126.3,126.1,125.9,125.4,121.4,115.2,35.3,31.1；HRMS(pos.ESI):m/z[M+H]+for C20H19ClNO2 calcd:340.1099,found:340.1133。
example 12
The reactants are N-p-phenylbenzoyl indole-3-formaldehyde and N-chlorosuccinimide, and the product is 3l of N-p-phenylbenzoyl-4-chloroindole-3-formaldehyde compound.
3l of N-p-phenylbenzoyl-4-chloroindole-3-formaldehyde compound, wherein the yield is 40%; a white solid; melting point 198 and 200 ℃;1H NMR(400MHz,CDCl3)δ10.82(s,1H),8.38(d,J＝8.2Hz,1H),8.17(s,1H),7.81(dd,J＝21.6,8.4Hz,4H),7.66(d,J＝7.4Hz,2H),7.51(t,J＝7.4Hz,2H),7.45(dd,J＝11.2,5.2Hz,2H),7.39(t,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ187.1,168.4,146.4,139.4,138.0,133.0,131.0,130.4,129.1,128.7,127.7,127.4,126.4,126.2,126.0,125.4,121.7,115.2；HRMS(pos.ESI):m/z[M+H]+for C22H15ClNO2 calcd:360.0786,found:360.0815。
example 13
The reactants are N-p-fluorobenzoyl indole-3-formaldehyde and N-chlorosuccinimide, and the product is N-p-fluorobenzoyl-4-chloroindole-3-formaldehyde compound 3 m.
3m of N-p-fluorobenzoyl-4-chloroindole-3-formaldehyde compound, wherein the yield is 67 percent; a white solid; melting point 148-;1H NMR(400MHz,CDCl3)δ10.79(s,1H),8.31(d,J＝8.4Hz,1H),8.06(s,1H),7.80(dd,J＝8.8,5.2Hz,2H),7.45(d,J＝8.0Hz,1H),7.38(t,J＝8.0Hz,1H),7.27(t,J＝8.4Hz,2H)；13C NMR(100MHz,CDCl3)δ186.9,167.4,165.7(d,JC-F＝254.9Hz),137.9,132.5,132.4(d,JC-F＝9.2Hz),128.7(d,JC-F＝3.2Hz),126.4,126.2,126.1,125.3,121.8,116.5(d,JC-F＝22.2Hz),115.1；HRMS(pos.ESI):m/z[M+H]+for C16H10ClFNO2 calcd:302.0379,found:302.0376。
example 14
The reactants are N-p-chlorobenzoyl indole-3-formaldehyde and N-chlorosuccinimide, and the product is N-p-chlorobenzoyl-4-chloroindole-3-formaldehyde compound 3N.
N-p-chlorobenzoyl-4-chloroindole-3-carbaldehyde compoundSubstance 3n, yield 48%; a white solid; melting point 154-;1H NMR(400MHz,CDCl3)δ10.82(s,1H),8.36(dd,J＝8.0,0.8Hz,1H),8.07(s,1H),7.73(d,J＝8.4Hz,2H),7.59(d,J＝8.4Hz,2H),7.48(dd,J＝7.6,0.8Hz,1H),7.42(t,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ186.9,167.5,140.0,137.9,132.4,131.0,130.9,129.5,126.5,126.2,126.1,125.4,121.9,115.1；HRMS(pos.ESI):m/z[M+H]+for C16H10Cl2NO2calcd:318.0083,found:318.0085。
example 15
The reactants are N-p-trifluoromethyl benzoyl indole-3-formaldehyde and N-chlorosuccinimide, and the product is N-p-trifluoromethyl benzoyl-4-chloroindole-3-formaldehyde compound 3 o.
3o of N-p-trifluoromethylbenzoyl-4-chloroindole-3-formaldehyde compound, wherein the yield is 42 percent; a white solid; melting point 186-188 deg.C;1H NMR(400MHz,CDCl3)δ10.80(s,1H),8.40(d,J＝8.0Hz,1H),7.98(s,1H),7.87(s,4H),7.48(d,J＝7.6Hz,1H),7.42(t,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ186.9,167.4,137.8,135.9,134.8(q,JC-F＝33.0Hz),132.1,129.8,127.3,126.8,126.4,126.2(q,JC-F＝3.6Hz),125.4,123.3(q,JC-F＝271.4Hz),122.3,115.3；HRMS(pos.ESI):m/z[M+H]+for C17H10ClF3NO2 calcd:352.0347,found:352.0349。
example 16
The reactants are N-m-toluoyl indole-3-formaldehyde and N-chlorosuccinimide, and the product is N-m-toluoyl-4-chloroindole-3-formaldehyde compound 3 p.
N-m-toluoyl-4-chloroindoleIndole-3-formaldehyde compound 3p with a yield of 79%; a yellow solid; melting point 158-;1H NMR(400MHz,CDCl3)δ10.79(s,1H),8.35(dd,J＝8.2,0.6Hz,1H),8.08(s,1H),7.55(s,1H),7.50(t,J＝8.4Hz,2H),7.44(t,J＝8.0Hz,2H),7.36(t,J＝8.0Hz,1H),2.46(s,3H)；13C NMR(100MHz,CDCl3)δ187.0,168.8,139.2,137.9,134.1,133.1,132.6,130.0,128.9,126.7,126.3,126.1,126.0,125.4,121.6,115.2,21.4；HRMS(pos.ESI):m/z[M+H]+for C17H13ClNO2 calcd:298.0629,found:298.0616。
example 17
The reactants are N-m-chlorobenzoyl indole-3-formaldehyde and N-chlorosuccinimide, and the product is N-m-chlorobenzoyl-4-chloroindole-3-formaldehyde compound 3 q.
3q of N-m-chlorobenzoyl-4-chloroindole-3-formaldehyde compound, wherein the yield is 30 percent; a white solid; melting point 192-;1H NMR(400MHz,CDCl3)δ10.81(s,1H),8.37(d,J＝8.0Hz,1H),8.04(s,1H),7.75(s,1H),7.67(d,J＝8.0Hz,1H),7.60(d,J＝7.6Hz,1H),7.53(t,J＝7.6Hz,1H),7.47(d,J＝7.6Hz,1H),7.41(t,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ187.0,167.3,137.9,135.5,134.3,133.3,132.3,130.4,129.5,127.4,126.7,126.3,125.4,122.1,115.3；HRMS(pos.ESI):m/z[M+H]+for C16H10Cl2NO2 calcd:318.0083,found:318.0092。
example 18
The reactants are N- (1-naphthoyl) indole-3-formaldehyde and N-chlorosuccinimide, and the product is N- (1-naphthoyl) -4-chloroindole-3-formaldehyde compound 3 r.
3r of N- (1-naphthoyl) -4-chloroindole-3-formaldehyde compound, wherein the yield is 54 percent; yellow colourA colored solid; melting point 190-;1H NMR(400MHz,CDCl3)δ10.74(s,1H),8.58(d,J＝8.0Hz,1H),8.11(d,J＝8.0Hz,1H),7.98(d,J＝8.0Hz,1H),7.86(d,J＝8.4Hz,1H),7.80(s,1H),7.66(d,J＝6.4Hz,1H),7.59(t,J＝7.6Hz,2H),7.55(dd,J＝11.2,4.2Hz,1H),7.48(d,J＝7.2Hz,1H),7.44(t,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ187.0,168.9,137.7,133.7,132.9,132.5,130.4,130.2,128.9,128.2,127.3,127.2,126.7,126.3,126.2,125.6,124.7,124.3,122.0,115.6；HRMS(pos.ESI):m/z[M+H]+for C20H13ClNO2 calcd:334.0629,found:334.0610。
example 19
The reactants are N- (2-naphthoyl) indole-3-formaldehyde and N-chlorosuccinimide, and the product is N- (2-naphthoyl) -4-chloroindole-3-formaldehyde compound 3 s.
N- (2-naphthoyl) -4-chloroindole-3-formaldehyde compound 3s, the yield is 35 percent; a white solid; melting point 187-188 ℃;1H NMR(400MHz,CDCl3)δ10.82(s,1H),8.39(d,J＝8.2Hz,1H),8.27(s,1H),8.17(s,1H),8.03(d,J＝8.4Hz,1H),7.96(d,J＝8.4Hz,2H),7.80(dd,J＝8.4,1.4Hz,1H),7.69(t,J＝7.6Hz,1H),7.63(t,J＝7.6Hz,1H),7.47(d,J＝7.8Hz,1H),7.40(t,J＝8.0Hz,1H)；13C NMR(100MHz,CDCl3)δ187.1,168.7,138.0,135.3,133.1,132.2,131.3,129.6,129.3,129.2,129.1,128.0,127.6,126.4,126.2,126.0,125.4,125.0,121.7,115.2；HRMS(pos.ESI):m/z[M+H]+for C20H13ClNO2calcd:334.0629,found:334.0629。
example 20
The reactants are N-benzoyl-5-fluoroindole-3-formaldehyde and N-chlorosuccinimide, and the product is N-benzoyl-4-chloro-5-fluoroindole-3-formaldehyde compound 3 t.
3t of N-benzoyl-4-chloro-5-fluoroindole-3-formaldehyde compound, wherein the yield is 26 percent; a white solid; melting point 169-171 ℃;1H NMR(400MHz,CDCl3)δ10.77(s,1H),8.37(dd,J＝9.0,4.2Hz,1H),8.13(s,1H),7.76–7.74(m,2H),7.71(t,J＝7.6Hz,1H),7.59(t,J＝7.6Hz,2H),7.29(d,J＝9.2Hz,1H)；13C NMR(100MHz,CDCl3)δ186.4,168.5,156.2(d,JC-F＝243.6Hz),134.1,133.7,133.4,132.3,129.9,129.6,129.2,121.8(d,JC-F＝3.1Hz),116.2(d,JC-F＝8.3Hz),114.4(d,JC-F＝24.6Hz),112.6(d,JC-F＝24.2Hz)；HRMS(pos.ESI):m/z[M+H]+for C16H10ClFNO2 calcd:302.0379,found:302.0377。
example 21
The reactants are N-benzoyl-6-methylindole-3-formaldehyde and N-chlorosuccinimide, and the product is N-benzoyl-4-chloro-6-methylindole-3-formaldehyde compound 3 u.
3u of N-benzoyl-4-chloro-6-methylindole-3-formaldehyde compound, wherein the yield is 80 percent; a yellow solid; melting point 122-124 ℃;1H NMR(400MHz,CDCl3)δ10.75(s,1H),8.20(s,1H),8.00(s,1H),7.75–7.73(m,2H),7.68(tt,J＝7.6,1.2Hz,1H),7.57(t,J＝7.8Hz,2H),7.28(s,1H),2.51(s,3H)；13C NMR(100MHz,CDCl3)δ187.1,168.8,138.2,137.2,133.2,132.7,132.4,129.6,129.1,127.3,125.6,123.1,121.6,115.4,21.6；HRMS(pos.ESI):m/z[M+H]+for C17H13ClNO2 calcd:298.0629,found:298.0612。
example 22
The reactants are N-benzoyl-6-methoxyindole-3-formaldehyde and N-chlorosuccinimide, and the product is N-benzoyl-4-chloro-6-methoxyindole-3-formaldehyde compound 3 v.
3v of N-benzoyl-4-chloro-6-methoxyindole-3-formaldehyde compound, wherein the yield is 44%; a white solid; melting point 173-174 ℃;1H NMR(400MHz,CDCl3)δ10.73(s,1H),7.97(d,J＝2.4Hz,1H),7.96(s,1H),7.74(dd,J＝7.2,1.2Hz,2H),7.69(t,J＝7.6Hz,1H),7.58(t,J＝7.6Hz,2H),7.10(d,J＝2.4Hz,1H),3.91(s,3H)；13C NMR(100MHz,CDCl3)δ187.0,169.0,158.8,138.7,133.2,132.7,131.8,129.5,129.1,126.4,121.7,119.2,115.4,99.4,56.1；HRMS(pos.ESI):m/z[M+H]+for C17H13ClNO3 calcd:314.0578,found:314.0607。
example 23
The reactants are N-benzoyl-6-chloroindole-3-formaldehyde and N-chlorosuccinimide, and the product is N-benzoyl-4, 6-dichloroindole-3-formaldehyde compound 3 w.
3w of N-benzoyl-4, 6-dichloroindole-3-formaldehyde compound, wherein the yield is 23 percent; a white solid; melting point 153-155 ℃;1H NMR(400MHz,CDCl3)δ10.75(s,1H),8.45(d,J＝1.6Hz,1H),8.08(s,1H),7.75(dd,J＝7.2,1.2Hz,2H),7.71(t,J＝7.2Hz,1H),7.60(t,J＝7.6Hz,2H),7.49(d,J＝1.6Hz,1H)；13C NMR(100MHz,CDCl3)δ186.4,168.4,137.9,133.5,133.3,132.1,132.0,129.6,129.2,126.5,126.3,124.0,121.5,115.6；HRMS(pos.ESI):m/z[M+H]+for C16H10Cl2NO2 calcd:318.0083,found:318.0062。
example 24
The reactants are N-benzoyl-7-methylindole-3-formaldehyde and N-chlorosuccinimide, and the product is N-benzoyl-4-chloro-7-methylindole-3-formaldehyde compound 3 x.
3x of N-benzoyl-4-chloro-7-methylindole-3-formaldehyde compound, wherein the yield is 43 percent; a white solid; melting point 122-124 ℃;1H NMR(400MHz,CDCl3)δ10.82(s,1H),8.03(s,1H),7.93(d,J＝7.2Hz,2H),7.74(t,J＝7.4Hz,1H),7.59(t,J＝7.8Hz,2H),7.37(d,J＝8.0Hz,1H),7.17(d,J＝8.0Hz,1H),2.40(s,3H)；13C NMR(100MHz,CDCl3)δ；187.3,167.2,137.5,134.6,134.1,131.8,130.9,129.3,128.6,126.1,125.8,124.8,123.8,121.1,21.0；HRMS(pos.ESI):m/z[M+H]+for C17H13ClNO2calcd:298.0629,found:298.0611。
the above-mentioned embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements of the technical solution of the present invention by those skilled in the art should fall within the protection scope defined by the claims of the present invention without departing from the spirit of the present invention.
Claims (3)
- A preparation method of a 1.4-site chloroindole compound is characterized by comprising the following steps:reacting the compound shown in the formula 1 with N-chlorosuccinimide (NCS) in an organic solvent under the participation of a guide group, an acid additive and a catalyst to obtain the 4-chloro indole compound; the reaction formula is as follows:
wherein R is selected from hydrogen and C1~C8Alkyl radical, C1~C8Alkoxy, halogen; PG is selected from the group consisting of benzoyl, p-toluoyl, p-methoxybenzoyl, p-tert-butylbenzoyl, p-phenylbenzoyl, p-fluorobenzoyl, p-chlorobenzoyl, p-trifluoromethylbenzoyl, m-toluoyl, m-chlorobenzoyl, 1-naphthoyl, 2-naphthoyl, acetyl, benzyloxycarbonyl (Cbz), p-formacylBenzenesulfonyl, methanesulfonyl, p-nitrobenzenesulfonyl, furoyl, thenoyl;wherein the organic solvent is chlorobenzene or 1, 2-dichloroethane; the catalyst is palladium acetate; the guide group is 2-amino-4-nitrobenzoic acid; the acid additive is trifluoroacetic acid. - 2. The method of claim 1, wherein: the molar ratio of the compound shown in the formula 1 to the N-chlorosuccinimide is 1:1 to 1: 2.
- 3. The method of claim 1, wherein: the reaction temperature was 50 ℃ and the reaction time was 24 hours.
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2020
- 2020-05-27 CN CN202010464178.7A patent/CN112028813B/en active Active
Non-Patent Citations (7)
| Title |
|---|
| CAS RN：1260889-89-1;ACS;《STN-Registry数据库》;20110127 * |
| CAS RN：1824293-40-4;ACS;《STN-Registry数据库》;20151207 * |
| Design and synthesis of novel N-sulfonyl-2-indoles that behave as 5-HT6 receptor ligands with significant selectivity for D3 over D2 receptors;Oscar M. Saavedra，等;《Bioorganic & Medicinal Chemistry》;20161012;第25卷;38-52 * |
| Diverse ortho-C(sp2)-H Functionalization of Benzaldehydes Using Transient Directing Groups;Xi-Hai Liu，等;《J. Am. Chem. Soc.》;20161222;第139卷;888-896 * |
| Palladium-catalyzed ortho-C(sp2)-H bromination of benzaldehydes via a monodentate transient directing group strategy;Qiyun Yong，等;《Tetrahedron Letters》;20191014;第60卷;151263 * |
| Synthesis of Fluorenones from Benzaldehydes and Aryl Iodides: Dual C-H Functionalizations Using a Transient Directing Group;Xiao-Yang Chen，等;《Org. Lett.》;20170222;第19卷;1140-1143 * |
| 过渡金属催化吲哚碳氢键直接官能化合成吲哚衍生物研究;邝广华;《江西师范大学硕士研究生学位论文》;20201115;全文 * |
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