Dihydrobenzo[b,e]pyrroloazepine heterocycles and methods for their preparation

Abstract

The present invention provides a novel electrochemical synthesis method for the production of novel dihydrobenzo[b,e]pyrroloazepine heteroheterocycles containing maleimide and tetrahydroquinoline heterocycles using a specially designed olefin known as 2-amino substituted benzylidene derivative as a starting material. Seven-membered N-containing heterocycles, especially 1-benzazepine, are indispensable structures of many biologically active compounds such as antidepressants, anticonvulsants, anti-HIV drugs, etc. The present method provides an oxidant-free and metal-free method for the synthesis of a class of novel dihydrobenzo[b,e]pyrroloazepine heteroheterocycles containing maleimide / succinamide, benzazepine and tetrahydroisoquinoline and other cyclic / acyclic amines by electrochemical C(sp 3 )‑H functionalization followed by tandem cyclization using readily available reagents. A unique, efficient, environmentally friendly, economical and safe technology has been developed to accelerate the novel synthesis method. The method includes simple electrochemical synthesis of dihydrobenzo[b,e]pyrroloazepine derivatives at ambient temperature using suitable electrodes and electrolytes. The synthesis employs an environmentally friendly electrochemical method that does not require transition metals and exogenous oxidants. The method is efficient and scalable, contributing to the realization of atom economy and step economy in the method. Therefore, the method is of substantial significance. The method provides a novel route for the synthesis of new backbones that can be used as potential biologically active heterocyclic backbones with photophysical relevance, including chemical sensors for the detection of picric acid and other nitro compounds.

Description

Technical Field

[0001] This invention relates to a dihydrobenzo[b,e]pyrroloza hybrid of formula 2. In particular, this invention relates to an efficient, environmentally friendly, cost-effective, and safe electrochemical method for synthesizing the dihydrobenzo[b,e]pyrroloza hybrid of formula 2. More particularly, this invention relates to the dihydrobenzo[b,e]pyrroloza hybrid of formula 2, which can be used as a potentially bioactive heterocyclic skeleton with photophysical correlations, including chemiluminescence sensors for detecting picric acid and other nitro compounds in water. Background of the Invention Seven-membered nitrogen-containing heterocycles, particularly 1-benzodiazepines, are important and indispensable structural cores in many bioactive molecules, including several marketed antidepressants such as fedovapagon, tolvaptan, mozavaptan, conivaptan, benazepril, zilpaterol, carbamazepine, mianserin, and mirtazapine, as well as veterinary drugs. Furthermore, molecules containing this core structure exhibit anticonvulsant, anti-HIV-1, and anti-allergic properties.

[0003] Previous literature reports consistently indicate that the synthesis of benzo[b,e]pyrrolo[a]aza hybrids typically involves the use of acids or transition metal catalysts, along with harmful oxidants, high temperatures, and prolonged reaction times. In most reported cases, harsh reaction conditions and expensive reagents are required, and no route is provided for the synthesis of novel dihydrobenzo[b,e]pyrrolo[a]aza hybrids containing a maleimide-benzo[b,e]pyrrolo[a]aza hybrid fused framework. In fact, no direct route exists for the synthesis of dihydrobenzo[b,e]pyrrolo[a]aza hybrids that allows for the rapid preparation of these hybrids from readily available starting materials; this problem is solved by the present invention.

[0004] See patent application "KR101396095B1", which describes the synthesis of numerous novel dipyrrolobenzodiazepines and explores their applications in the pharmaceutical field. Compared to their monomeric counterparts, these dipyrrolobenzodiazepines exhibit significant advantages due to their unique ability to interact with DNA in the minor groove.

[0005] See patent application “US 9,006,231 B2”, which provides valuable insights into the synthesis of innovative thiazolinone derivatives. Furthermore, this patent provides for the development of pharmaceutical compositions comprising compounds derived from this invention. These compositions are being explored for potential applications in treating a variety of medical conditions, including proliferative diseases such as cancer, autoimmune diseases, inflammatory diseases, and diabetic retinopathy.

[0006] See patent application “IE47146B1”, which provides detailed information on the synthesis of pyrrolo(2,1-b)(3) benzo[a]za derivatives as antipsychotics, antiserotonins, and antihistamines. These derivatives are suitable for administration to patients requiring treatment in these therapeutic classes.

[0007] See journal " Chem. Pharm. Bull. 2004, 52 (5), 577-590”, in which Seto’s group, while exploring potential CCR5 antagonists, began to synthesize a series of biologically active 1-benzodiazepine compounds. Through chemical modification of the 1-benzodiazepine skeleton, compounds that showed significant inhibitory activity against HIV-1 in ENV-mediated membrane fusion assays were identified.

[0008] See journal " Bioorg. Med. Chem. Lett. 2007, 17 In the series “4630-4634”, the Hoyt group reported the synthesis and evaluation of benzodiazepines and benzodiazepine ketones as potential sodium channel blockers.

[0009] Synthetic routes are described as mainly falling into three categories (schemes): a) negative hydrogen migration / cyclization strategies; b) metal-free cyclization strategies; and c) transition metal-catalyzed cyclization strategies. Representative examples of each method are discussed below to highlight their advantages and disadvantages.

[0010] The concept of negative hydrogen migration reaction has been used by several research groups to synthesize 7-membered N-heterocycles.

[0011] (a) See journal " J. Am. Chem. Soc. 2011, 133 "2100-2103", in which Seidel's group used this concept to synthesize indole containing a seven-membered nitrogen heterocycle using aminobenzaldehyde and indole. During the same period, Zhang's group reported a pioneering method. They employed a Lewis acid-catalyzed intramolecular domino reaction, utilizing the concept of 1,5-negative hydrogen migration / cyclization to synthesize tetrahydroquinoline and tetrahydroazahexane ( Chem. Commun., 2010 , 46,6593–6595). In 2015, Xu's group developed 1,2-pyrrole-ringed benzoza heterocyclic compounds under redox neutral conditions using a dehydration / 1,5-negative hydrogen migration / cyclization strategy. Eur. J. Org. Chem. 2015, 2015 (6727-6733). An organocatalytic [1,5]-hydrogen migration / cyclization strategy for the synthesis of dihydrodibenzo[b,e]-nitrogen compounds was developed. This work demonstrates the ability of in-situ generated carbocations as catalysts to drive tandem hydrogen migration processes to construct complex molecules ( Org. Lett. 2018, 20 , 1 (138–141). However, it is important to note that all of these methods require the presence of acid or metal catalysts, as well as toxic solvents and high temperatures. While these methods provide valuable insights, these factors pose challenges in terms of safety and scalability for industrial applications.

[0012] (b) See the journal " Tetrahedron ,2005, 61 , 8241–8248”, in which the Preobrazhenskaya group used a TFA solution of CH3SO3H to synthesize 12b,13-dihydro-4bH-indolo[3,2-d]pyrrolo[3,4-b][1]benzozaza-5,7(6H,8H)-dione derivatives. The Evans group introduced a multi-step method for synthesizing azazaza-heterocyclic compounds ( Org. Biomol. Chem .,2011, 9 (3886–3895). This method involves the synthesis of the key intermediate trans-1-aryl-7,11b-dihydro-1H-aziridinido[1,2a]dibenzo[c,f]azazadimethylbenzene via a series of steps. Initially, isomerization with dichloroaziridinidoside is performed, followed by intramolecular Friedel-Crafts acylation of the attached benzene ring under SnCl4 catalysis. Subsequently, hydride-induced intramolecular cyclization occurs. These aziridinidoside, as precursors to heterocyclic azomethyl base ylides, readily undergo 1,3-dipolar cycloaddition with dipolarophiles to form dibenzo[c,f]pyrrolo[1,2-a]azazadimethylbenzene derivatives. See journal " Tetrahedron Lett ,2013, 54 ", 1765–1767", in which the synthesis of tricyclic nitrogen heterocyclic compounds involves nitrogen heterocyclization reactions, which are carried out by free amines and α,β The condensation of unsaturated ketones proceeds, followed by a sequential reduction step. This study also investigated the cyclization reactions of conjugated esters and imides using the same conditions. Notably, when using… α,β In the case of unsaturated esters, the only result is a Michael addition reaction, leading to the formation of a seven-membered ring.

[0013] When these reactions are used for large-scale industrial production, significant drawbacks associated with them include the use of acid catalysts, oxidants and reductants, toxic solvents, and high temperatures.

[0014] (c) See the journal "Org. Lett. 2004, 6, 2785–2788", in which the Yamaguchi research group developed a RhCp for the lactamation of amino alcohols. Significant progress has been made in catalytic methods. These methods have proven to be versatile, capable of synthesizing lactams with five-, six-, or seven-membered benzo[a]-fused rings. However, significant challenges remain. The primary catalyst used in the reaction is quite expensive, and the reaction conditions require elevated temperatures. These factors constitute considerable obstacles when considering the applicability of this method in industrial-scale synthesis. Furthermore, the range of substrates available for benzo[a]-a]-a]-a]-a]-a]-a]-a]]]]] catalytic method] is not provided in the original text and can be omitted.)

[0015] See the journal "Chem. Commun., 2017, 53, 12229-12232", where Wang's group introduced a copper-catalyzed method involving the oxidative cross-coupling of C(sp3)–H and C(sp2)–H bonds to promote the synthesis of 1-benzodiazepines. This method requires the use of toxic silver salts and bases, as well as high temperatures and extended reaction times. These factors collectively constitute obstacles when considering the feasibility of implementing this method on an industrial scale.

[0016] Existing synthetic methods for preparing benzo[a]aza derivatives have several drawbacks, such as the need for expensive transition metal catalysts, toxic oxidants, multi-step operations, and high temperatures. Notably, there is a significant gap in the search for direct routes to synthesize potentially biologically active benzo[a]aza derivatives.

[0017] In most of the reported cases, harsh reaction conditions and expensive reagents are required, and no route is provided for the synthesis of such novel dihydrobenzo[b,e]pyrrolo-aza hybrids containing maleimide and benzo[b,e]pyrrolo-aza hybrid skeletons.

[0018] Despite significant progress in synthetic chemistry, the synthesis of benzo[a]aza units and their subsequent incorporation into cyclic imides or tetrahydroisoquinolines and other cyclic / acyclic amines remain challenging due to the complexity of the polycyclic fused benzo[a]aza skeleton.

[0019] This invention employs an electrochemical synthesis method to synthesize dihydrobenzo[b,e]pyrroloza heterocycles containing maleimide / succinamide, benzozaza, tetrahydroisoquinoline / tetrahydroquinoline, and other cyclic / acyclic amines. This method is characterized by its high efficiency, environmental friendliness, economy, and safety. Notably, this method eliminates the need for transition metals, bases, and sacrificial hazardous oxidants in the reaction. Furthermore, this electrochemical synthesis can be conveniently carried out at ambient temperatures.

[0020] The starting material for the synthetic design, namely the 2-amino-substituted benzyl group, is also readily prepared in a single step. Against this backdrop, this introduces a highly efficient and scalable electrochemical method for the preparation of dihydrobenzo[b,e]pyrroloza nitrogen compounds. This method not only promises efficient synthesis but also fits well with potential industrial production methods and exhibits photophysical properties for detecting nanomolar concentrations of picric acid and other nitro compounds in water.

[0021] The purpose of this invention The main objective of this invention is to provide a dihydrobenzo[b,e]pyrrolo-nitrogen hybrid of formula 2.

[0022] Another object of the present invention is to provide a direct and cost-effective method for synthesizing, in a single step, dihydrobenzo[b,e]pyrroloza hybrids of formula 2 containing maleimide / succinamide, benzozazaza, tetrahydroisoquinoline, and other cyclic / acyclic amines.

[0023] Another object of the present invention is to provide a sustainable, environmentally friendly, and commercially viable cost-effective electrochemical method for electrochemically converting C(sp) 3 )-H functionalization was followed by tandem cyclization to synthesize the dihydrobenzo[b,e]pyrroloza heterohydride of formula 2.

[0024] Another object of the present invention is to use a suitable and effective electrolyte in a suitable solvent or solvent mixture for the electrochemical synthesis of dihydrobenzo[b,e]pyrroloza hybrids of formula 2.

[0025] Another object of the present invention is to provide a method for synthesizing dihydrobenzo[b,e]pyrroloza hybrids of formula 2 in the absence of transition metals, Lewis acids and conventional sacrificial oxidants.

[0026] Another object of the present invention is to provide a dihydrobenzo[b,e]pyrrolo-nitro-azo hybrid of formula 2 as a novel photophysical small molecule probe for the detection of picric acid and other nitro compounds. Attached Figure Description

[0027] Figure 1This indicates the direct synthesis of the dihydrobenzo[b,e]pyrroloza hybrid of Formula 2 from the 2-amino-substituted benzyl compound of Formula 1.

[0028] Figure 2 (A) The change in emission intensity of 2 mL of 10 µM 2a THF-water (10:3) solution with PA gradually added during excitation at 350 nm. (B) Quenching efficiency diagram of 2a.

[0029] Figure 3 The Stern-Volmer plot shows the results after the addition of picric acid for 2 years.

[0030] Figure 4 The graph shows the limit of detection (LoD) for picric acid in 2a (standard deviation σ = 6750.8).

[0031] Figure 5 (A) The change in emission intensity of 2 mL of 10 µM 2b THF-water (10:3) solution under 352 nm excitation with gradual addition of PA. (B) Quenching efficiency of 2b.

[0032] Figure 6 The Stern-Volmer plot of 2b after the addition of picric acid is shown.

[0033] Figure 7 The graph shows the limit of detection (LoD) for picric acid in 2b (standard deviation σ = 7922.2).

[0034] Figure 8 (A) The change in emission intensity of a 2 mL 10 µM 2e THF-water (10:3) solution under 325 nm excitation with gradual addition of PA. (B) The quenching efficiency of 2e.

[0035] Figure 9 The Stern-Volmer plot shows the 2e after the addition of picric acid.

[0036] Figure 10 The graph shows the limit of detection (LoD) for picric acid (standard deviation σ = 17150.6).

[0037] Figure 11 (A) The change in emission intensity of 2 mL of 10 µM 2f THF-water (10:3) solution with PA gradually added under 352 nm excitation. (B) Quenching efficiency diagram of 2f.

[0038] Figure 12 The Stern-Volmer plot shows the results after 2 hours of adding picric acid.

[0039] Figure 13 The graph shows the limit of detection (LoD) for picric acid in 2f (standard deviation σ = 8378.1).

[0040] Figure 14 (A) The change in emission intensity of 2 mL of 10 µM 2t THF-water (10:3) solution under 350 nm excitation with gradual addition of PA. (B) Quenching efficiency diagram of 2t.

[0041] Figure 15 The Stern-Volmer plot shows the results after adding picric acid for 2 days.

[0042] Figure 16 The graph shows the limit of detection (LoD) for picric acid at 2t (standard deviation σ = 10126.6).

[0043] Figure 17 (A) The change in emission intensity of 2 mL of 10 µM 2v THF-water (10:3) solution under 350 nm excitation with gradual addition of PA. (B) Quenching efficiency diagram for 2v.

[0044] Figure 18 The Stern-Volmer plot shows the result of adding picric acid to 2v.

[0045] Figure 19 The graph shows the limit of detection (LoD) for picric acid at 2v (standard deviation σ = 8271.7).

[0046] Figure 20 (A) The change in emission intensity of 2 mL of 10 µM 2b in THF-water (10:3) solution with gradual addition of 2,4-DNP under 352 nm excitation. (B) Quenching efficiency of 2b.

[0047] Figure 21 (A) The change in emission intensity of 2 mL of 10 µM 2b THF-water (10:3) solution under 352 nm excitation with gradual addition of NB. (B) Quenching efficiency diagram of 2b.

[0048] Figure 22 (A) The change in emission intensity of 2 mL of 10 µM 2b THF-water (10:3) solution with 4-NP gradually added under 352 nm excitation. (B) Quenching efficiency diagram of 2b.

[0049] Figure 23 (A) The change in emission intensity of 2 mL of 10 µM 2b THF-water (10:3) solution under 352 nm excitation with gradual addition of 1,3-DNB. (B) Quenching efficiency of 2b.

[0050] Figure 24 (A) The change in emission intensity of 2 mL of 10 µM 2b THF-water (10:3) solution under 352 nm excitation with gradual addition of 2,4-DNT. (B) Quenching efficiency of 2b. Summary of the Invention

[0051] Therefore, the present invention provides a compound of formula 2. in R 1 and R 2 Independently selected from the group consisting of: hydrogen, straight-chain or branched (C1-C12) alkyl, perfluoro(C1-C12) alkyl, (C3-C12) cycloalkyl, (C6-C12) bicycloalkyl, (C3-C14) tricycloalkyl, (C6-C10) aryl; perfluoro(C6-C10) aryl, perfluoro(C6-C10) aryl(C1-C3) alkyl, (C5-C10) heteroaryl, (C5 -C10) heteroaryl (C1-C3) alkyl, hydroxyl, (C1-C12) alkoxy, (C3-C12) cycloalkoxy, (C6-C12) bicycloalkoxy, (C7-C14) tricycloalkoxy, (C6-C10) aryloxy (C1-C3) alkyl, (C6-C10) aryloxy, (C5-C10) heteroaryloxy, (C1-C6) acyloxy, halogen, nitro or amino; R 3 Independently selected from the group consisting of: hydrogen, halogen-containing aryl, nitro, amino, all kinds of organic functional groups, straight-chain or branched (C1-C12) alkyl, perfluoro(C1-C12) alkyl, (C3-C12) cycloalkyl, (C6-C12) bicycloalkyl, (C3-C14) tricycloalkyl, (C6-C10) aryl; perfluoro(C6-C10) aryl, perfluoro(C6-C10) aryl(C1-C3) alkyl. alkyl, (C5-C10)heteroaryl, (C5-C10)heteroaryl, (C1-C3)alkyl, hydroxyl, (C1-C12)alkoxy, (C3-C12)cycloalkoxy, (C6-C12)bicycloalkoxy, (C7-C14)tricycloalkoxy, (C6-C10)aryloxy, (C1-C3)alkyl, (C6-C10)aryloxy, (C5-C10)heteroaryloxy, (C1-C6)acyloxy; n = 0, 1, 2, 3, 4 or 5; X = C or N.

[0052] In yet another embodiment of the invention, the representative compound of Formula 2 is selected from the group consisting of: i.6-Phenyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2a); ii.6-(4-methoxyphenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2b); iii. 6-(4-bromophenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2c); iv. 6-(4-fluorophenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-zircono[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2d); v.6-(4-(trifluoromethyl)phenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2e); vi. 6-(3,4,5-trimethoxyphenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2f); vii. 6-Benzyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2g); viii. 6-Methyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2h); ix.6-Ethyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2i); x.6-propyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2j); xi.6-hexyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2k); xii. 6-Heptyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2l); xiii. 6-Octy-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2m); xiv. 6-(2-methoxyethyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2n); XV. 3-(5,7-dioxo-4c,5,14,15-tetrahydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-aziro[2,1-a]isoquinoline-6(7H)-yl)propionate ethyl ester (2o); xvi.10-Chloro-6-ethyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2p); xvii.10-Chloro-6-phenyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2q); xviii.6-Benzyl-11-chloro-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2r); xix.3-Methyl-6-phenyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2s); xx.2,3-Dimethoxy-6-phenyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2t); xxi.2,3-Dimethoxy-6-methyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2u); xxii.2,3-Dimethoxy-6-(3,4,5-trimethoxyphenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2v); xxiii.6-(4-phenylbutyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2w); xxiv.6-Phenylacetyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2x); xxv.6-(2-(thiophen-2-yl)ethyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-zirco[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2y); xxvi.6-(3-methoxyphenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2z); xxvii.6-Phenyl-14,15-dihydro-4bH-pyrido[3',2':6,7]pyrrolo[3',4':3,4]aza-zircono[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2za); xxviii.6-(4-chlorophenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2zb); xxix.11-Phenyl-1,2,3,12b-tetrahydrobenzo[f]dipyrrolo[1,2-a:3',4'-c]azapyridine-10,12(11H,12aH)-dione(2zc); xxx.11-(p-Tolyl)-1,2,3,12b-tetrahydrobenzo[f]dipyrrolo[1,2-a:3',4'-c]aza-10,12(11H,12aH)-dione(2zd); xxxi.11-(3,4,5-trimethoxyphenyl)-1,2,3,12b-tetrahydrobenzo[f]dipyrrolo[1,2-a:3',4'-c]azapyridine-10,12(11H,12aH)-dione(2ze); xxxii.11-Benzyl-1,2,3,12b-tetrahydrobenzo[f]dipyrrolo[1,2-a:3',4'-c]aza-10,12(11H,12aH)-dione(2zf).

[0053] In another embodiment, the present invention provides an electrochemical method for synthesizing compound of formula 2, comprising the following steps: i. Mix Formulas 3, 4, and 5 with the solvent in a round-bottom flask equipped with an electromagnetic stirrer to obtain a mixture; Where R 1 R 2 and R 3 Same as defined above.

[0054] ii. Stir the mixture obtained in step (i) for a period of time ranging from 12 to 24 hours to obtain a solid precipitate; iii. Filter the solid precipitate obtained in step (ii) and then wash with cold ethanol to obtain the compound of formula 1; iv. Add Formula 1, electrolyte, optionally along with electrocatalyst and organic solvent to a 5 mL oven-dried electrochemical reaction vial, using a graphite rod as both anode and cathode, to obtain a mixture; v. The mixture obtained in step (iv) is then electrolyzed at ambient temperature with a constant current of 1 mA or 1-10 mA for a period of time ranging from 10 h to 24 h to obtain the compound of formula 2.

[0055] In yet another embodiment of the invention, the electrolyte used is selected from the group consisting of: ammonium salts of Formula 6, tetrabutylammonium tetrafluoroborate (TBABF4), tetrabutylammonium hexafluorophosphate (TBAPF6), tetrabutylammonium perchlorate (TBAClO4), tetrabutylammonium iodide (TBAI), tetrabutylammonium bromide (TBAB), tetrabutylammonium acetate (TBAOAc), ammonium acetate (NH4OAc), ammonium iodide (NH4I), or quaternary ammonium alkaloids or metal salts.

[0056] Formula 6 Where R = hydrogen, straight-chain or branched (C1-C12) alkyl, perfluoro(C1-C12) alkyl, (C3-C12) cycloalkyl, (C6-C12) bicycloalkyl, (C3-C14) tricycloalkyl, (C6-C10) aryl; perfluoro(C6-C10) aryl, perfluoro(C6-C10) aryl(C1-C3) alkyl, (C5-C10) heteroaryl, (C5-C10) Heteroaryl (C1-C3)alkyl, hydroxyl, (C1-C12)alkoxy, (C3-C12)cycloalkoxy, (C6-C12)bicycloalkoxy, (C7-C14)tricycloalkoxy, (C6-C10)aryloxy, (C1-C3)alkyl, (C6-C10)aryloxy, (C5-C10)heteroaryloxy, (C1-C6)acyloxy, halogen, nitro or amino.

[0057] In yet another embodiment of the invention, the metal salt used is selected from the group consisting of: lithium perchlorate (LiClO4), sodium perchlorate (NaClO4), lithium chloride (LiCl), sodium chloride (NaCl), potassium chloride (KCl), potassium iodide (KI), sodium iodide (NaI), potassium fluoride (KF), potassium phosphate, sodium acetate (NaOAc), and magnesium chloride (MgCl2).

[0058] In yet another embodiment of the invention, the organic solvent used is selected from the group consisting of: TFE, MeOH, 1,4-dioxane, toluene, benzene, acetonitrile, THF, 2-MeTHF, dimethylformamide (DMF), dimethyl sulfoxide, ethyl acetate or acetone, alone or in combination thereof, preferably TFE / MeOH.

[0059] In yet another embodiment of the invention, the electrocatalyst used is selected from the group consisting of ABNO, ferrocene, PIDA, or TEMPO.

[0060] In yet another embodiment of the invention, the compound of formula 1 is selected from the group consisting of: i.( E )-3-(2-(3,4-dihydroisoquinoline-2(1 H )-yl)benzylidene)-1-phenylpyrrolidine-2,5-dione (1a); ii. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(4-methoxyphenyl)pyrrolidine-2,5-dione (1b); iii. (E)-1-(4-bromophenyl)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)pyrrolidine-2,5-dione (1c); iv. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(4-fluorophenyl)pyrrolidine-2,5-dione (1d); v.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-(4-(trifluoromethyl)phenyl)pyrrolidine-2,5-dione(1e); vi. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-(3,4,5-trimethoxyphenyl)pyrrolidine-2,5-dione (1f); vii.( E )-1-benzyl-3-(2-(3,4-dihydroisoquinoline-2(1 H )-yl)benzylidene)pyrrolidine-2,5-dione (1g); viii. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-methylpyrrolidine-2,5-dione (1h); ix.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-ethylpyrrolidine-2,5-dione (1i); x.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-propylpyrrolidine-2,5-dione (1j); xi.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-hexylpyrrolidine-2,5-dione(1k); xii.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-heptylpyrrolidine-2,5-dione (1l); xiii.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-octylpyrrolidine-2,5-dione(1m); xiv.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-(2-methoxyethyl)pyrrolidine-2,5-dione(1n); xv.(E)-3-(3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-2,5-dioxopyrrolidone-1-yl)ethyl propionate (1o); xvi.(E)-3-(5-chloro-2-(3,4-dihydroisoquinolin-2(1H)-yl)benzyl)-1-ethylpyrrolidine-2,5-dione(1p); xvii.(E)-3-(5-chloro-2-(3,4-dihydroisoquinolin-2(1H)-yl)benzyl)-1-phenylpyrrolidine-2,5-dione(1q); xviii.( E )-1-benzyl-3-(4-chloro-2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)pyrrolidine-2,5-dione(1r); xix.(E)-3-(2-(7-methyl-3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-phenylpyrrolidine-2,5-dione(1s); xx.( E )-3-(2-(6,7-dimethoxy-3,4-dihydroisoquinoline-2(1 H )-yl)benzylidene)-1-phenylpyrrolidine-2,5-dione (1t); xxi.(E)-3-(2-(6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-methylpyrrolidine-2,5-dione (1u); xxii.A(E)-3-(2-(6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(3,4,5-trimethoxyphenyl)pyrrolidine-2,5-dione(1v); xxiii.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(4-phenylbutyl)pyrrolidine-2,5-dione (1w); xxiv.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-phenylethylpyrrolidine-2,5-dione (1x); xxv.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(2-(thiophen-2-yl)ethyl)pyrrolidine-2,5-dione(1y); xxvi.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(3-methoxyphenyl)pyrrolidine-2,5-dione (1z); xxvii.(E)-3-((2-(3,4-dihydroisoquinoline-2(1H)-yl)pyridin-3-yl)methylene)-1-phenylpyrrolidine-2,5-dione(1za); xxviii.(E)-1-(4-chlorophenyl)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)pyrrolidine-2,5-dione (1zb); xxix.(E)-1-phenyl-3-(2-(pyrrolidone-1-yl)benzylidene)pyrrolidone-2,5-dione (1zc); xxx.(E)-3-(2-(pyrrolidine-1-yl)benzylidene)-1-(p-tolyl)pyrrolidine-2,5-dione (1zd); xxxi.(E)-3-(2-(pyrrolidine-1-yl)benzylidene)-1-(3,4,5-trimethoxyphenyl)pyrrolidine-2,5-dione (1ze); xxxii.(E)-1-benzyl-3-(2-(pyrrolidine-1-yl)benzylidene)pyrrolidine-2,5-dione (1zf); xxxiii.(E)-1-phenyl-3-(2-(4-phenylpiperazin-1-yl)benzylidene)pyrrolidine-2,5-dione (1 ozg); xxxiv.3-(2-(azacycloheptane-1-yl)benzylidene)-1-benzylpyrrolidine-2,5-dione (1zh); xxxv.(E)-3-(2-(cyclohexyl(methyl)amino)benzylidene)-1-phenylpyrrolidine-2,5-dione (1zi) xxxvi.3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(4-nitrophenyl)pyrrolidine-2,5-dione (1zj); xxxvii.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)pyrrolidine-2,5-dione (1zk); xxxviii.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(4-(dimethylamino)phenyl)pyrrolidine-2,5-dione (1zl); xxxix.(E)-2-(4-(3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-2,5-dioxopyrrolidine-1-yl)phenyl)-6-(dimethylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione (1zm).

[0061] In yet another embodiment of the invention, the yield of the compound of formula 1 is in the range of 40%-90%.

[0062] In yet another embodiment of the invention, the yield of the compound of formula 2 is in the range of 40%-87%.

[0063] In yet another embodiment of the invention, the compounds of Formula 2 and Formula 1 can be used as potential bioactive molecules and as potential molecular probes and chemical sensors for detecting picric acid and other nitro compounds. Detailed Implementation

[0064] This invention provides a dihydrobenzo[b,e]pyrroloza heterostructure of Formula 2, which can be used as a potentially bioactive heterocyclic skeleton and has photophysical relevance, including for the detection of picric acid and other nitro compounds: Where R 1 and R 2 Independently selected from the group consisting of: hydrogen, straight-chain or branched (C1-C12) alkyl, perfluoro(C1-C12) alkyl, (C3-C12) cycloalkyl, (C6-C12) bicycloalkyl, (C3-C14) tricycloalkyl, (C6-C10) aryl; perfluoro(C6-C10) aryl, perfluoro(C6-C10) aryl(C1-C3) alkyl, (C5-C10) heteroaryl, (C (5-C10) heteroaryl(C1-C3)alkyl, hydroxyl, (C1-C12)alkoxy, (C3-C12)cycloalkoxy, (C6-C12)bicycloalkoxy, (C7-C14)tricycloalkoxy, (C6-C10)aryloxy(C1-C3)alkyl, (C6-C10)aryloxy, (C5-C10) heteroaryloxy, (C1-C6) acyloxy, halogen or amino.

[0065] R 3 Independently selected from the group consisting of: hydrogen, halogen-containing aryl, nitro, amino, all kinds of organic functional groups, straight-chain or branched (C1-C12) alkyl, perfluoro(C1-C12) alkyl, (C3-C12) cycloalkyl, (C6-C12) bicycloalkyl, (C3-C14) tricycloalkyl, (C6-C10) aryl; perfluoro(C6-C10) aryl, perfluoro(C6-C10) aryl(C1-C3) alkyl. alkyl, (C5-C10)heteroaryl, (C5-C10)heteroaryl, (C1-C3)alkyl, hydroxyl, (C1-C12)alkoxy, (C3-C12)cycloalkoxy, (C6-C12)bicycloalkoxy, (C7-C14)tricycloalkoxy, (C6-C10)aryloxy, (C1-C3)alkyl, (C6-C10)aryloxy, (C5-C10)heteroaryloxy, (C1-C6)acyloxy.

[0066] n is selected from 0, 1, 2, 3, 4 or 5; X is selected from C or N.

[0067] This invention further provides a direct and efficient synthetic method for synthesizing dihydrobenzo[b,e]pyrroloza hybrids of formula 2, particularly starting from readily available starting materials. This is achieved by seamlessly fusing pharmaceutically valuable maleimides and tetrahydroisoquinoline, along with other cyclic amines, to form dihydrobenzo[b,e]za hybrids of formula 2. This method involves electrochemical imine ion formation followed by tandem cyclization. These derivatives play a crucial role as building blocks and are widely found in a variety of natural products.

[0068] The current method has been extended to synthesize a library of 7-membered dihydrobenzo[b,e]pyrrolo-nitro-hetero ...

[0069] Existing synthetic methods for preparing benzo[a]aza derivatives have several drawbacks, such as the need for expensive transition metal catalysts, toxic oxidants, multi-step operations, and high temperatures. Notably, there is a significant gap in the search for direct routes for synthesizing novel potentially bioactive and bioprobe benzo[a]aza derivatives.

[0070] This invention provides an electrochemical method for synthesizing dihydrobenzo[b,e]pyrroloza hybrids of Formula 2 containing maleimide / succinamide, benzozaza, tetrahydroisoquinoline, and other cyclic / acyclic amines from starting materials (Formula 1).

[0071] This invention provides a method for synthesizing a dihydrobenzo[b,e]pyrrolo-azo hybrid of formula 2 using an ortho-amino-substituted benzyl group of starting material of formula 1.

[0072] The starting material of Formula 1, the o-amino-substituted benzylidene, is readily prepared in a single step via the corresponding aldehyde and tetrahydroisoquinoline, as well as other cyclic / acyclic amines. The method for preparing Formula 1 comprises the following steps: i. Mix the compound of formula 3, the compound of formula 4, the compound of formula 5 and the solvent into a round-bottom flask equipped with an electromagnetic stirrer; ii. Stir the mixture continuously for 12-24 hours to obtain a solid precipitate.

[0073] iii. Filter out the solid precipitate and wash it with cold ethanol to obtain the compound of formula 1.

[0074] The preparation of dihydrobenzo[b,e]pyrroloza heteropolymers and their derivatives from compound [(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-pyrrolidine-2,5-dione] of formula 1 includes the following steps: i. A 5 mL oven-dried electrochemical reaction vial is filled with an ammonium salt of formula 1, TBABF4, or any formula 6, an electrocatalyst (ABNO, ferrocene, PIDA, TEMPO), a metal salt as an electrolyte (0.2 mmol, 2.0 equivalent), and TFE / MeOH (1:1, 2.0 mL) or any other combination of organic solvents, such as 1,4-dioxane, toluene, benzene, acetonitrile, THF, 2-MeTHF, dimethylformamide (DMF), dimethyl sulfoxide, ethyl acetate, or acetone, preferably TFE / MeOH.

[0075] Formula 6 Where R = hydrogen, straight-chain or branched (C1-C12) alkyl, perfluoro(C1-C12) alkyl, (C3-C12) cycloalkyl, (C6-C12) bicycloalkyl, (C3-C14) tricycloalkyl, (C6-C10) aryl; perfluoro(C6-C10) aryl, perfluoro(C6-C10) aryl(C1-C3) alkyl, (C5-C10) heteroaryl, (C5-C10) Heteroaryl (C1-C3)alkyl, hydroxyl, (C1-C12)alkoxy, (C3-C12)cycloalkoxy, (C6-C12)bicycloalkoxy, (C7-C14)tricycloalkoxy, (C6-C10)aryloxy, (C1-C3)alkyl, (C6-C10)aryloxy, (C5-C10)heteroaryloxy, (C1-C6)acyloxy, halogen, nitro or amino.

[0076] ii. Equip the vial with graphite rods as both anode and cathode (immersion surface area 1.2 × 0.5 cm²). 2 (or any surface area) or any other electrode, with the distance between the electrodes being 0.6 cm or 0.3-100 cm.

[0077] iii. Stir and electrolyze the resulting mixture at ambient temperature with a constant current of 1 mA or 1-10 mA for 10 h or until the reaction is complete.

[0078] iv. After the reaction was indicated by TLC, the evaporation was evaporated under vacuum and the crude product was purified directly on silica gel (230-400 mesh) by column chromatography (using ethyl acetate / petroleum ether (10%)) to give product formula 2 (yield = 85%; Rf = 0.2) and up to 87% of other impurities.

[0079] This method involves the electrochemical formation of imineonium, followed by a tandem cyclization step. Through this innovative approach, the present invention provides a practical route for producing 2-dihydrobenzo[b,e] nitrogen-containing hybrids with a fused tricyclic structure.

[0080] The synthetic method of this invention is relatively simple to operate, has mild reaction conditions, and produces good yields (up to 87%). Subsequent separation and / or purification of the product is direct. The method uses evaporation of the volatiles under vacuum, and the crude product is purified directly by silica gel (230-400 mesh) column chromatography (using ethyl acetate / petroleum ether).

[0081] The compounds of Formula 2 and Formula 1 have been identified as potential probes for the detection of picric acid and other nitro compounds.

[0082] To explore the potential bioanalytical applications of these molecules, the excitation and emission properties of 2e were investigated. The results showed that the excitation and emission wavelengths were 315 nm and 484 nm, respectively. Subsequently, the fluorescence quenching of compounds 2a, 2b, 2e, 2f, 2t, and 2v in the presence of picric acid and other nitro compounds was studied. Notably, picric acid induced a significant decrease in the emission intensity of these compounds in aqueous solution (THF:H₂O, 10:3), demonstrating promising detection capabilities with detection limits ranging from 53 to 3.8 nM and quenching constants ranging from 1.7 x 10⁻⁶. 4 Up to 6.2 x 10 4 M -1 .

[0083] Photophysical studies of Formula 2 for the detection of picric acid and other nitro compounds.

[0084] Example The following examples are given by way of illustration only and should not be construed as limiting the scope of the invention.

[0085] Example 1 General procedure for preparing formula 2 [(4bS,4cR)-6-phenyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione] Milligram-level reaction To a 5 mL oven-dried electrochemical reaction vial, add (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-phenylpyrrolidine-2,5-dione (39.4 mg, 0.1 mmol), TBABF4 or any ammonium salt as the electrolyte (0.2 mmol, 2.0 equivalent), and TFE / MeOH (1:1, 2.0 mL) or any other organic solvent combination, such as 1,4-dioxane, toluene, benzene, acetonitrile, THF, 2-MeTHF, dimethylformamide (DMF), dimethyl sulfoxide, ethyl acetate, or acetone, preferably TFE / MeOH. Equip the vial with graphite rods as the anode and cathode, with a distance of 0.6 cm between the electrodes (immersion surface area 1.2 × 0.5 cm²). 2 Or any other electrode with a distance of 0.6 cm or 0.3-100 cm between electrodes. The resulting mixture was stirred and electrolyzed at a constant current of 1 mA for 10 h at ambient temperature, or stirred and electrolyzed at a constant current of 1-10 mA for 10 h at ambient temperature, or until the reaction was complete. After the reaction was indicated by TLC, the evaporation was evaporated under vacuum, and the crude product was purified directly on silica gel (230-400 mesh) by column chromatography (using ethyl acetate / petroleum ether (10%)) to give product 2a (34 mg; yield = 85%; Rf = 0.2).

[0086] Gram-scale reaction An oven-dried 20 mL electrochemical reaction vial was packed with (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-phenylpyrrolidine-2,5-dione 1a (1 g, 2.5 mmol), TBABF4 (5.0 mmol, 2.0 equivalent), or any ammonium salt as the electrolyte and TFE / MeOH (1:1, 12 mL) or any other organic solvent combination, 1,4-dioxane, toluene, benzene, acetonitrile, THF, 2-MeTHF, dimethylformamide (DMF), dimethyl sulfoxide, ethyl acetate, or acetone, preferably TFE / MeOH. The vial was fitted with graphite rods as the anode and cathode, with an electrode distance of 0.6 cm or any other electrode distance of 0.6 cm or 0.3–100 cm. The resulting mixture was stirred and electrolyzed at a constant current of 2 mA for 24 h at ambient temperature. After the reaction was indicated by TLC, the evaporation was evaporated under vacuum, and the crude product was purified directly on silica gel (230-400 mesh) by column chromatography (using ethyl acetate / petroleum ether (10%)) to give product 2a (700 mg; yield = 71%; Rf = 0.2).

[0087] We have followed the procedure described above for the synthesis of formula 2a-2zf.

[0088] General procedure for preparing dihydrobenzo[b,e]pyrrolo-azo hybrids of formula 2 To a 5 mL oven-dried Electrasyn vial, add a substituted benzylidene 1 (0.1 mmol), TABF4 (0.2 mmol, 2.0 equivalent), or any ammonium salt as the electrolyte, electrocatalyst (ABNO, ferrocene, PIDA, TEMPO), and TFE / MeOH (1:1, 2.0 mL) or any other organic solvent combination, such as 1,4-dioxane, toluene, benzene, acetonitrile, THF, 2-MeTHF, dimethylformamide (DMF), dimethyl sulfoxide, ethyl acetate, or acetone, preferably TFE / MeOH. Equip the vial with graphite rods as the anode and cathode, with a distance of 0.6 cm between the electrodes (immersion surface area 1.2 × 0.5 cm²). 2 Or any other electrode with a distance of 0.6 cm or 0.3-100 cm between electrodes. The resulting mixture was stirred and electrolyzed at a constant current of 1 mA for 10 h at ambient temperature. After the reaction was indicated by TLC, the evaporation was evaporated under vacuum, and the crude product was purified directly on silica gel (230-400 mesh) by column chromatography (using ethyl acetate / petroleum ether (10%)) to give product 2.

[0089] Example 1 6-Phenyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2a): yellow solid (33.3 mg, 85% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp = 164–166 °C; 1H NMR (400 MHz, chloroform-d) δ 7.81 (d, J = 2.3 Hz, 1H), 7.52 (dd, J = 7.8, 1.5 Hz, 1H), 7.46 – 7.37 (comp, 3H), 7.36 – 7.29 (comp, 5H), 7.24 – 7.20 (m, 1H), 7.10 (d, J = 8.4 Hz,1H), 7.00 – 6.93 (comp, 2H), 4.04 (d, J = 6.7 Hz, 1H), 3.86 (td, J = 10.6,4.3 Hz, 1H), 3.73 (dd, J = 6.7, 2.3 Hz, 1H), 3.69 – 3.62 (m, 1H), 3.25 – 3.18(m, 1H), 3.08 (dt, J = 15.5, 4.7 Hz, 1H).; 13C NMR (101 MHz, chloroform-d) δ 171.1,169.0, 150.2, 136.9 (X 2), 135.8, 135.2, 135.1, 133.5, 131.7, 129.2 (X 2), 129.0, 127.7, 126.5 (X 2), 126.4, 125.7, 121.3, 119.8, 118.0 (X 2), 61.0, 54.0, 48.5, 28.5.; HRMS (ESI, m / z) for C26H21N2O2 [M+H]+: calculated value 393.1603, measured value 393.1590.

[0090] (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-phenylpyrrolidine-2,5-dione (1a): Yellow solid (295.5 mg, 75% yield); Rf 0.30 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 144–146 °C; single diastereomer; ¹H NMR (400 MHz, chloroform-d) δ 8.12 (t, J = 2.3 Hz, 1H), 7.53–7.48 (comp, 3H), 7.43–7.39 (comp, 4H), 7.22–7.10 (comp, 6H), 4.30 (s, 2H), 3.76 (d, J = 2.4 Hz, 2H), 3.28 (t, J = 5.8 Hz, 2H), 3.06 (t, J = 5.7 Hz, 2H); ¹³C NMR (101 MHz, chloroform-d) δ 173.3,170.1, 153.3, 134.4, 134.3, 133.0, 132.1, 131.0, 129.0, 129.0, 128.4, 127.5,126.4, 126.4, 126.4, 126.3, 125.9, 122.4, 122.0, 119.2, 53.4, 53.0, 34.0,29.3; HRMS (ESI, m / z) Calculated value for C26H23N2O2 [M+H]+ is 395.1760, measured value is 395.1761.

[0091] Example 2 6-(4-Methoxyphenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2b): yellow solid (29.6 mg, 69% yield); Rf 0.20 (petroleum ether / ethyl acetate = 5:1); column chromatographic eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) 1H δ 7.79 (d, J = 2.3 Hz, 1H), 7.51 (dd, J = 7.9, 1.5 Hz, 1H), 7.37 (ddd, J = 8.6,7.2, 1.7 Hz, 1H), 7.31 – 7.28 (comp, 2H), 7.26 (s, 1H), 7.25 – 7.18 (comp,2H), 7.09 (d, J = 8.3 Hz, 1H), 6.99 – 6.97 (m, 1H), 6.96 – 6.93 (comp, 2H),4.03 (d, J = 6.7 Hz, 1H), 3.86 - 3.82 (m, 2H), 3.81 (s, 3H), 3.71 (dd, J =6.8, 2.3 Hz, 1H), 3.68 – 3.61 (m, 1H), 3.21 (ddd, J = 19.9, 9.7, 4.8 Hz, 1H), 3.11 – 3.04 (s, 1H).; 13C NMR (101 MHz, chloroform-d) δ 171.2, 169.2, 159.2, 150.0, 136.8, 135.5, 135.1, 133.4, 131.6, 129.1, 127.9, 127.6, 127.6 (X 2), 126.3, 125.7, 124.7, 121.3, 119.7, 117.9, 114.2 (X 2), 60.8, 55.4, 53.8, 48.4, 28.4.HRMS (ESI, m / z) For C27H22N2O3 [M+H]+, the calculated value is 423.1709, and the measured value is 423.1715.

[0092] (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(4-methoxyphenyl)pyrrolidine-2,5-dione (1b) Brown solid (300.0 mg, 71% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 92–94 °C; single diastereomer; ¹H NMR (400 MHz, chloroform-d) δ 8.10 (t, J = 2.2 Hz, 1H), 7.51 – 7.48 (m, 1H), 7.44 – 7.38 (m, 1H), 7.32 (app d, J = 9.0 Hz, 2H), 7.20 (d, J = 8.3 Hz, 2H), 7.18 – 7.16 (comp, 2H), 7.13 – 7.09 (dd, J = 9.9, 5.3 Hz, 2H). 7.02 – 6.99 (comp, 2H), 4.29 (s, 2H),3.84 (s, 3H), 3.74 (d, J = 2.3 Hz, 2H), 3.27 (t, J = 5.8 Hz, 2H), 3.05 (t, J= 5.7 Hz, 2H).; 13C NMR (101 MHz, chloroform-d) δ 173.6, 170.4, 159.4, 153.3,134.4, 134.3, 132.9, 131.0, 129.1 (X 2), 127.6 (X 3), 126.4, 126.3, 125.9,122.4, 122.1, 119.2, 114.4 (X 3), 55.5, 53.4, 53.0, 34.0, 29.3. Example 3 6-(4-Bromophenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2c): yellow solid (29.6 mg, 69% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; 1H NMR (400 MHz, chloroform-d) δ 7.83 (d, J = 2.3 Hz, 1H), 7.56 (dd, J = 8.0, 4.0 Hz, 2H), 7.52 (dd, J = 8.0, 4.0 Hz, 1H). 7.41 - 7.39 (m, 1H), 7.33 - 7.29 (comp, 2H), 7.27(app s, 1H), 7.24 (d, J = 3.1 Hz, 1H), 7.22 (dd, J = 6.8, 1.9 Hz, 1H), 7.09(d, J = 8.4 Hz, 1H), 7.01 – 6.91 (comp, 2H), 4.02 (d, J = 6.7 Hz, 1H), 3.87 (dt, J = 10.4, 5.1 Hz, 1H), 3.72 (dd, J = 6.7, 2.3 Hz, 1H), 3.65 (dt, J =11.1, 4.8 Hz, 1H), 3.25 – 3.16 (m, 1H), 3.08 (dt, J = 15.6, 4.7 Hz, 1H). ¹³C NMR (101 MHz, chloroform-d) δ 170.7, 168.5, 150.1, 136.9, 136.2, 135.1, 133.3, 132.1 (X²), 131.8, 131.0, 129.1, 128.0, 127.8, 127.7 (X²), 126.3, 125.1, 121.9, 121.1, 119.8, 117.8, 60.8, 53.9, 48.4, 28.3. HRMS (ESI, m / z) The calculated value for C26H19BrN2O2 [M]+ is 470.0630, while the measured value is 470.0619.

[0093] (E)-1-(4-bromophenyl)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)pyrrolidine-2,5-dione (1c): yellow solid (250.0 mg, 30% yield); Rf 0.30 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 116–118℃; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 8.12 (t, J = 2.5 Hz, 1H), 7.66 – 7.58 (m, 2H), 7.49 (d, J = 7.8 Hz, 1H), 7.45– 7.39 (m, 1H), 7.37 – 7.31 (m, 2H). 7.23 – 7.07 (comp, 4H), 7.14 – 7.09 (comp, 2H) 4.29 (s, 2H), 3.75 (d, J = 2.5 Hz, 2H), 3.27 (t, J = 5.9 Hz, 2H), 3.04 (t, J = 5.8 Hz, 2H).; 13C NMR (101 MHz, chloroform-d) δ 173.0, 169.8, 153.2,134.3, 134.3, 133.5, 132.2, 132.2, 131.2, 131.1, 129.1, 127.8, 127.4, 126.5,126.3, 126.0, 122.5, 122.2, 121.6, 119.3, 53.4, 53.0, 34.0, 29.3.; HRMS (ESI, m / z) for C26H21BrN2O2 [M]+: calculated value 472.0786, measured value 472.0786.

[0094] Example 4 6-(4-Fluorophenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2d): yellow solid (25.9 mg, 63% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; 1H NMR (400 MHz, chloroform-d) δ 7.80 (d, J = 2.3 Hz, 1H), 7.52 (dd, J = 7.8, 1.5 Hz, 1H), 7.41 – 7.36 (m, 1H), 7.35 –7.33 (m, 1H), 7.33 – 7.32 (m, 1H), 7.31 (d, J = 3.5 Hz, 1H), 7.25 – 7.21 (m,1H), 7.15 – 7.07 (comp, 3H), 7.01 – 6.92 (comp, 2H), 4.03 (d, J = 6.7 Hz,1H), 3.86 (td, J = 10.6, 4.2 Hz, 1H), 3.72 (dd, J = 6.7, 2.3 Hz, 1H), 3.65(dt, J = 11.1, 4.8 Hz, 1H), 3.24 - 3.17 (m, 1H), 3.08 (dt, J = 15.5, 4.6 Hz,1H).13C NMR (101 MHz, chloroform-d) δ 171.0, 168.8, 163.1, 160.64, 150.1, 136.9, 136.0, 135.1, 133.3, 131.7, 129.1, 128.2, 128.1, 128.0, 127.6, 126.3, 125.2, 121.1, 119.7, 117.8, 116.0, 115.8, 60.8, 53.9, 48.4, 28.4. 19F NMR (376 MHz, chloroform-d) δ -112.79. HRMS (ESI, m / z) for C26H19FN2O2 [M]+ Calculated value: 410.1431; Measured value: 410.1436.

[0095] (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-(4-fluorophenyl)pyrrolidine-2,5-dione (1d): yellow solid (250.0 mg, 50% yield); Rf 0.30 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 112–114 °C; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 8.12 (t, J = 2.4 Hz, 1H), 7.75 – 7.61 (m, 1H), 7.60 – 7.53 (m, 1H), 7.52 – 7.45 (m, 1H), 7.44 – 7.37 (comp, 2H), 7.24 – 13C NMR (101 MHz, chloroform-d) δ 173.2, 170.0, 153.3, 134.4,134.3, 133.3, 131.1, 129.1 (X 2), 128.5, 128.4, 128.2, 128.2, 127.5, 126.5,126.3, 126.0, 122.5, 121.8, 119.3, 116.2, 115.9, 53.4, 53.1, 34.0, 29.3; 19F NMR (376 MHz, chloroform-d) δ -112.47. Example 5 6-(4-(trifluoromethyl)phenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2e): yellow solid (40.1 mg, 87% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 166–168℃; 1H NMR (400MHz, chloroform-d) δ 7.83 (d, J = 2.3 Hz, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.56–7.50 (m, 3H), 7.42–7.38 (m, 1H), 7.34 – 7.29 (comp, 2H), 7.25 – 7.21 (m,1H), 7.10 (d, J = 8.4 Hz, 1H), 7.01 – 6.92 (m, 2H), 4.04 (d, J = 6.6 Hz, 1H), 3.87 (td, J = 10.6, 4.3 Hz, 1H), 3.75 (dd, J = 6.7, 2.3 Hz, 1H), 3.70 – 3.63(m, 1H), 3.26 – 3.17 (m, 1H), 3.09 (dt, J = 15.6, 4.7 Hz, 1H).13C NMR (101MHz, Chloroform-d) δ 170.6, 168.4, 150.1, 137.0, 136.5 (X 2), 135.1, 133.2, 131.9, 129.0, 128.1, 127.7, 126.5 (X 3), 126.3 (X 2), 126.0, 124.0, 124.9, 121.1, 119.8, 117.9, 60.9, 53.9, 48.4, 28.3. HRMS (ESI, m / z) for C27H19F3N2O2 [M]+: calculated value 460.1399, measured value 460.1397.

[0096] (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-(4-(trifluoromethyl)phenyl)pyrrolidine-2,5-dione (1e): yellow solid (194.0 mg, 42% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:3); column chromatography eluent, petroleum ether / EtOAc = 10:3; mp 104–106 °C; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 8.15 (t, J = 2.4 Hz, 1H), 7.76 (d, J = 8.3 Hz, 2H), 7.61 (d, J = 8.2 Hz, 2H), 7.50 (dd, J = 7.8, 1.7 Hz, 1H), 7.48 – 7.41 (m, 1H), 7.24 – 7.18 (comp, 4H), 7.16 – 7.14 (m, 1H), 7.12 – 7.10 (m, 1H), 4.29 (s, 2H), 3.79 (d, J = 2.5 Hz, 2H), 3.28 (t, J = 5.8 Hz, 2H), 3.05 (s, 2H).; 13C NMR (101 MHz, chloroform-d) δ 172.8, 169.6, 153.4, 135.2, 135.1, 134.3, 134.2, 133.9, 131.3, 129.1 (X 2), 127.4, 126.6 (X 3), 126.5, 126.3, 126.2, 126.1, 126.0, 122.5, 121.4, 119.4, 53.5, 53.1, 34.0, 29.3; 19F NMR (376 MHz, chloroform-d) δ -62.60. Example 6 6-(3,4,5-trimethoxyphenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]azabenzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2f): yellow solid (30.9 mg, 64% yield); Rf 0.10 (petroleum ether / ethyl acetate = 5:1); column chromatographic eluent, petroleum ether / EtOAc = 5:1; mp 170-172℃; 1H NMR (400 MHz, chloroform-d) δ 7.80 (d, J = 2.3 Hz, 1H), 7.52 (dd, J = 7.9, 1.5 Hz, 1H), 7.39 (ddd, J = 8.6, 7.2, 1.6 Hz, 1H), 7.33 – 7.29 (m,2H), 7.21 (dt, J = 8.7, 4.3 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 7.01 – 6.92(m, 2H), 6.55 (s, 2H), 4.04 (d, J = 6.8 Hz, 1H), 3.90 – 3.86 (m, 1H), 3.84 (d, J = 3.8 Hz, 6H), 3.74 (dd, J = 6.8, 2.3 Hz, 1H), 3.66 (dt, J = 10.8, 4.8Hz, 1H), 3.21 (ddd, J = 14.7, 10.0, 4.4 Hz, 1H), 3.08 (dt, J = 15.5, 4.6 Hz, 1H). 13C NMR (101 MHz, chloroform-d) δ 171.2, 169.0, 153.3, 150.1, 137.9, 136.8, 135.8, 135.0, 133.3, 131.7, 129.1, 128.0, 127.7, 127.4, 126.3, 125.4, 121.2, 119.8, 117.9, 104.2 (X 3), 60.8, 56.1 (X 3), 53.9, 48.4, 28.4. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-(3,4,5-trimethoxyphenyl)pyrrolidine-2,5-dione (1f): yellow solid (290.4 mg, 60% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:3); column chromatography eluent, petroleum ether / EtOAc = 10:3; single diastereomer; mp 132–134 °C; 1H NMR (400 MHz, chloroform-d) δ 8.12 (t, J = 2.4 Hz, 1H), 7.50 (dd, J = 7.8, 1.8 Hz, 1H), 7.45–7.38 (m, 1H), 7.25–7.14 (comp, 5H), 7.13–7.07 (m, 1H), 6.62 (s, 2H), 4.30 (s, 2H), 3.87 (s, 9H), 3.75 (d, J = 2.5 Hz, 2H), 3.29 (t, J = 5.8 Hz, 2H), 3.06 (d, J = 5.8 Hz, 2H).; 13C NMR (101 MHz, chloroform-d) δ 173.4, 170.2, 153.5, 153.1, 138.2, 138.1, 134.4, 134.1, 133.1, 131.21, 129.16, 129.2, 127.5, 126.5, 126.3, 126.0, 122.7, 122.1, 119.5, 104.3 (X 3), 60.8, 56.3 (X 2), 53.5, 53.0, 34.0, 29.1. Example 7 6-Benzyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2 g): yellow solid (30.0 mg, 74% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; 1H NMR (400 MHz, chloroform-d) δ 7.67 (d, J = 2.2 Hz, 1H), 7.46 (dd, J = 7.8, 1.5 Hz, 1H), 7.39 (dd, J = 7.9, 1.5 Hz, 2H), 7.34 (ddd, J = 8.7, 7.2, 1.7) Hz, 2H), 7.31 – 7.26 (comp, 4H), 7.21 (td,J = 7.3, 1.3 Hz, 2H), 7.05 (d, J = 8.4 Hz, 1H), 6.96 – 6.91 (m, 1H), 6.79 (d,J = 7.5 Hz, 1H), 4.77 – 4.63 (m, 2H), 3.90 (d, J = 6.8 Hz, 1H), 3.82 (ddd, J = 11.1, 9.8, 4.4 Hz, 1H), 3.63 – 3.55 (m, 1H), 3.52 (dd, J = 6.8, 2.2 Hz,1H), 3.15 (ddd, J = 14.3, 9.7, 4.4 Hz, 1H), 3.05 (dt, J = 15.5, 4.8 Hz, 1H). 13C NMR (101 MHz, chloroform-d) δ 171.7, 169.5, 149.9, 136.7, 136.2, 135.1, 134.9, 133.4, 131.4, 129.1, 128.9 (X 2), 128.5 (X 2), 127.9, 127.8, 127.7, 126.2, 126.1, 121.2, 119.6, 117.9, 60.7, 53.7, 48.3, 42.1, 28.4. HRMS (ESI, The calculated value for C27H22N2O2 [M]+ is 406.1681 (m / z), while the measured value is 406.1901.

[0097] (E)-1-Benzyl-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)pyrrolidine-2,5-dione (1g) Yellow solid (306.0 mg, 75% yield); Rf 0.30 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 186-188℃; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 8.01 (app s, 1H), 7.47 (app d, J = 6.9 Hz, 2H), 7.44 – 7.29 (comp, 5H), 7.22 – 7.15 (comp, 4H), 7.12 – 7.08 (comp, 2H), 4.80 (s, 2H), 4.26 (s, 2H), 3.57 (d, J = 2.1 Hz, 2H), 3.24 (t, J = 5.7 Hz, 2H), 3.03 (t, J = 5.5 Hz, 2H); 13C NMR (101 MHz, chloroform-d) δ 173.9, 170.7, 153.1, 136.0, 134.4, 134.3, 132.1, 130.8, 129.0, 129.0, 129.0, 128.6, 127.9, 127.7, 126.4, 126.3, 125.9, 122.6, 122.4, 119.3, 53.5, 52.8, 42.4, 33.9, 29.1; HRMS (EI, m / z) for C27H24N2O2[M]+ Calculated value: 408.1838; measured value: 408.1842.

[0098] Example 8 6-Methyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2h): yellow solid (22.5 mg, 68% yield); Rf 0.20 (petroleum ether / ethyl acetate = 5:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) δ 7.68 (d, J = 2.2 Hz, 1H), 7.48 (dd, J = 7.8, 1.4 Hz, 1H), 7.38 – 7.29 (comp, 3H), 7.24 – 7.22 (m, 1H), 7.06 (d, J = 8.4 Hz, 1H). 6.97 – 6.92 (m, 1H), 6.89 (d, J = 7.5Hz, 1H), 3.94 (d, J = 6.9 Hz, 1H), 3.65 – 3.58 (m, 1H), 3.56 (dd, J = 6.9,2.2 Hz, 1H), 3.17 (ddd, J = 14.6, 10.0, 4.4 Hz, 1H), 3.07 (dd, J = 10.5, 5.8Hz, 1H), 3.03 (s, 3H).13C NMR (101 MHz, chloroform-d) δ 172.2, 170.1, 149.9, 136.7,135.1, 134.6, 133.5, 131.4, 129.1, 127.9, 127.6, 126.2, 126.1, 121.1, 119.6, 117.8, 60.5, 53.8, 48.3, 28.4, 24.7. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-methylpyrrolidine-2,5-dione (1h): Yellow solid (199.2 mg, 60% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 148–150 °C; single diastereomer; ¹H NMR (400 MHz, chloroform-d) δ 7.99 (t, J = 2.4 Hz, 1H), 7.44 (dd, J = 7.8, 1.8 Hz, 1H), 7.41 – 7.35 (m, 1H), 7.22 – 7.16 (comp, 4H), 7.14 – 7.07 (m, 1H), 4.27 (s, 2H), 3.57 (d, J = 2.6 Hz, 2H), 3.24 (t, J = 5.8 Hz, 2H). 3.13 (s, 3H), 3.03 (t, J = 5.8 Hz, 2H).; 13C NMR (101 MHz, chloroform-d) δ 174.4, 171.2, 153.1, 134.4, 134.3, 131.9, 130.8, 129.1, 129.0, 127.7, 126.4, 126.3, 125.9, 122.7, 122.4, 119.2, 53.4, 52.8, 33.8, 29.2, 24.8. Example 9 6-Ethyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2i): yellow solid (18.0 mg, 52% yield); Rf 0.20 (petroleum ether / ethyl acetate = 5:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) δ 7.67 (d, J = 2.3 Hz, 1H), 7.47 (dd, J = 7.8, 1.5 Hz, 1H), 7.38 – 7.28 (m, 3H), 7.23 (dd, J = 7.2, 1.6 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.98 – 6.91 (m, 1H), 6.87 (d, J= 7.5 Hz, 1H), 3.92 (d, J = 6.9 Hz, 1H), 3.82 (td, J = 10.5, 10.0, 4.3 Hz,1H), 3.68 – 3.50 (m, 4H), 3.18 (ddd, J = 14.5, 9.8, 4.4 Hz, 1H), 3.06 (dt, J= 15.5, 4.7 Hz, 1H), 1.17 (t, J = 7.2 Hz, 1H).13C NMR (101 MHz, chloroform-d) δ172.0, 169.8, 149.9, 136.7, 135.1, 134.5, 133.5, 131.4, 129.1, 127.9, 127.6, 126.3, 126.1, 121.2, 119.6, 117.8, 60.5, 53.8, 48.3, 33.5, 28.4, 13.3. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-ethylpyrrolidine-2,5-dione (1i): yellow solid (499.0 mg, 95% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 142–144 °C; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 7.98 (t, J = 2.4 Hz, 1H), 7.44 (dd, J = 7.8, 1.7 Hz, 1H), 7.41 – 7.34 (m, 1H), 7.18 (dd, J = 4.7, 3.0 Hz, 4H), 7.14 – 7.06 (m, 2H), 4.26 (s, 2H), 3.69 (q, J= 7.2 Hz, 2H), 3.55 (d, J = 2.5 Hz, 2H), 3.25 (t, J = 5.6 Hz, 2H), 3.03 (t, J= 5.9 Hz, 2H), 1.25 (t, J = 7.2 Hz, 3H).; 13C NMR (101 MHz, chloroform-d) δ 174.2,170.9, 153.1, 134.4, 131.7, 129.0, 129.0, 127.7, 126.4, 126.3 (X 2), 125.9,122.7, 122.4, 119.2, 53.4, 52.8, 33.8, 33.7, 29.2, 28.2, 13.2. Example 10 6-Propyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2j): yellow solid (27.7 mg, 77% yield); Rf 0.40 (petroleum ether / ethyl acetate = 5:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) δ 7.66 (d, J = 2.3 Hz, 1H), 7.47 (dd, J = 7.8, 1.6 Hz, 1H), 7.38 – 7.28 (comp, 2H), 7.23 (td, J = 7.3, 1.7 Hz, 1H), 7.06 (d, J = 8.3 Hz, 1H), 6.97 – 6.91 (m, 1H), 6.86 (d, J = 7.6 Hz, 1H), 3.92 (d, J = 6.8 Hz, 1H), 3.82 (td, J = 10.6, 10.1,4.3 Hz, 1H), 3.61 (dt, J = 11.2, 4.8 Hz, 1H), 3.56 – 3.45 (m, 2H), 3.18 (ddd,J = 14.7, 9.7, 4.6 Hz, 1H), 3.05 (dt, J = 15.5, 4.7 Hz, 1H), 1.61 (qd, J =7.5, 2.8 Hz, 3H), 0.89 (t, J = 7.4 Hz, 3H) 13C NMR (101 MHz, chloroform-d) δ 172.1, 170.0, 149.9, 136.7 (X 2), 135.1, 134.5, 131.3, 129.0, 127.9, 127.6, 126.3, 126.1, 121.2, 119.6, 117.8, 60.6, 53.7, 48.3, 40.1, 28.4, 21.2, 11.3. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-propylpyrrolidine-2,5-dione (1j): Yellow gel (216.0 mg, 60% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 7.98 (t, J = 2.4 Hz, 1H), 7.44 (dd, J = 7.8, 1.7 Hz, 1H), 7.41 – 7.34 (m, 1H), 7.18 (dd, J = 4.7, 3.0 Hz, 4H), 7.14 – 7.06 (m, 2H), 4.26 (s, 2H), 3.69 (q, J = 7.2 Hz, 2H), 3.55 (d, J = 2.5 Hz, 2H). 3.25 (t, J = 5.6 Hz, 2H), 3.03 (t, J = 5.9 Hz, 2H), 1.72 – 1.62 (m, 2H), 1.25 (t, J = 7.2 Hz, 3H).; 13C NMR (101 MHz, chloroform-d) δ 174.4, 171.1, 153.1, 134.4, 134.4, 131.8, 130.8, 129.1, 129.0, 127.8, 126.4, 126.3, 125.9, 122.7, 122.4, 119.2, 53.4, 52.8, 40.4, 33.8, 29.2, 21.3,11.4.; HRMS (ESI, m / z) for C23H24N2O2 [M]+: calculated value 360.1838, measured value 360.1842.

[0099] Example 11 6-Hexyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2k): yellow solid (24.0 mg, 60% yield); Rf 0.10 (petroleum ether / ethyl acetate = 5:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) δ 7.66 (d, J = 2.3 Hz, 1H), 7.47 (dd, J = 7.8, 1.6 Hz, 1H), 7.38 – 7.28 (comp, 2H), 7.23 (td, J = 7.3, 1.7 Hz, 1H), 7.06 (d, J = 8.3 Hz, 1H), 6.97 – 6.91 (m, 1H), 6.86 (d, J = 7.6 Hz, 1H), 3.92 (d, J = 6.8 Hz, 1H), 3.82 (td, J = 10.6, 10.1,4.3 Hz, 1H), 3.61 (dt, J = 11.2, 4.8 Hz, 1H), 3.64 – 3.46 (m, 4H), 3.18 (ddd,J = 14.7, 9.7, 4.6 Hz, 1H), 3.05 (dt, J = 15.5, 4.7 Hz, 1H), 1.58 – 1.55 (m,2H), 1.19 – 1.26 (m, 6H), 0.89 (t, J = 7.4 Hz, 3H). 13C NMR (101 MHz, chloroform-d) δ 172.1, 170.0, 149.9, 136.7, 135.1, 134.5, 133.5, 131.4, 129.1, 127.9, 127.6, 126.4, 126.1, 121.2, 119.6, 117.9, 60.7, 53.7, 48.3, 38.7, 31.3, 28.5, 27.9, 26.5, 22.5, 14.0. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-hexylpyrrolidine-2,5-dione(1k) Yellow gel (237.2 mg, 59% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 7.98 (t, J = 2.2 Hz, 1H), 7.44 (dd, J = 7.7, 1.3 Hz, 1H), 7.41 – 7.35 (m, 1H), 7.18 (dd, J = 4.3, 2.7 Hz, 4H), 7.13 – 7.08 (m, 2H), 4.27 (s, 2H), 3.65 – 3.59 (m, 2H), 3.55 (d, J = 2.3 Hz, 2H), 3.25 (t, J = 5.8 Hz, 2H), 3.03 (t, J = 5.7 Hz, 2H), 1.64 (p, J = 7.9, 7.5 Hz, 3H), 1.33 – 1.30 (m, 6H), 0.89 (t, J = 6.8 Hz, 3H).; 13C NMR (101 MHz, chloroform-d) δ 174.4, 171.1, 153.1, 134.40, 134.37, 131.7, 130.8, 129.05, 129.00, 127.7, 126.4, 126.3, 125.9, 122.7, 122.4, 119.2.53.4,52.8, 38.9, 33.8, 31.3, 29.2, 27.8, 26.6, 22.5, 14.0. Example 12 6-Heptyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2l): yellow solid (22.8 mg, 55% yield); Rf 0.10 (petroleum ether / ethyl acetate = 5:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) δ 7.66 (d, J = 2.3 Hz, 1H), 7.47 (dd, J = 7.8, 1.5 Hz, 1H), 7.37 – 7.34 (m, 1H), 7.33 – 7.28 (m, 2H), 7.23 (td, J = 7.4, 1.7 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.97 –6.92 (m, 1H), 6.86 (d, J = 7.5 Hz, 1H), 3.92 (d, J = 6.8 Hz, 1H), 3.82 (td, J= 10.6, 10.1, 4.3 Hz, 1H), 3.65 – 3.46 (m, 4H), 3.18 (ddd, J = 14.5, 9.9, 4.4Hz, 1H), 3.06 (dt, J = 15.5, 4.7 Hz, 1H), 1.61 – 1.54 (m, 2H), 1.29 – 1.24(m, 8H), 0.86 (t, J = 7.0 Hz, 1H). 13C NMR (101 MHz, chloroform-d) δ 172.1, 169.9, 149.9, 136.7, 135.1, 134.5, 133.5, 131.3, 129.1, 127.9, 127.6, 126.4, 126.1, 121.3, 119.6, 117.9, 60.7, 53.7, 48.3, 38.7, 31.7, 28.8, 28.5, 27.9, 26.8, 22.5, 14.0. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-heptylpyrrolidine-2,5-dione (1l) Yellow gel (166.4 mg, 40% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 7.98 (t, J = 2.3 Hz, 1H), 7.44 (dd, J = 7.8, 1.7 Hz, 1H), 7.37 (d, J = 8.2 Hz, 1H), 7.18 (dd, J = 4.2, 2.7 Hz, 4H), 7.13 – 7.05 (m, 2H), 4.27 (s, 2H), 3.67 – 3.59 (m, 2H), 3.55 (d, J = 2.5 Hz, 2H). 3.24 (d, J = 5.8 Hz, 2H), 3.03 (t, J = 6.0,2H), 1.64 (t, J = 7.3 Hz, 2H), 1.33 – 1.26 (m, 8H), 0.88 (t, J = 6.8 Hz,2H).; 13C NMR (101 MHz, Chloroform-d) δ 174.4, 171.1, 134.4, 131.7, 130.8, 129.1 (X2), 129.0, 127.8, 126.4, 126.3 (X 2), 125.9, 122.7, 122.4, 119.2, 53.4, 52.8,38.9, 33.8, 31.7, 29.2, 28.8, 27.9, 26.9, 22.6, 14.0.; HRMS (ESI, m / z) for C27H32N2O2 [M]+: calculated value 416.2464, measured value 416.2478.

[0100] Example 13 6-Octyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2m): yellow solid (19.3 mg, 45% yield); Rf 0.10 (petroleum ether / ethyl acetate = 5:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) δ 7.66 (d, J = 2.2 Hz, 1H), 7.47 (dd, J = 7.8, 1.5 Hz, 1H), 7.37–7.28 (comp, 3H), 7.23 (td, J = 7.4, 1.7 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.97 – 6.92 (m, 1H), 6.86 (d, J = 7.5 Hz, 1H), 3.92 (d, J = 6.8 Hz, 1H), 3.82(td, J = 10.5, 10.1, 4.3 Hz, 1H), 3.64 – 3.59 (m, 1H), 3.57 – 3.48 (m, 1H), 3.22 – 3.14 (m, 1H), 3.09 – 3.02 (m, 1H)), 1.58 – 1.57 (m, 3H), 1.26 – 1.25(comp, 1H), 0.86 (t, J = 6.8 Hz, 3H) 13C NMR (101 MHz, chloroform-d) δ 172.1, 149.9, 136.7, 135.1, 134.5, 133.6, 131.4, 129.1, 127.9, 127.6, 126.4, 126.1, 121.3, 119.6, 117.9, 60.7, 53.7, 48.3, 38.7, 31.7, 29.1, 28.5, 27.9, 26.9, 22.6, 14.1. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-octylpyrrolidine-2,5-dione(1m) Yellow gel (185.0 mg, 43% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 7.98 (t, J = 2.2 Hz, 1H), 7.44 (dd, J = 7.7, 1.2 Hz, 1H), 7.41 – 7.35 (m, 1H), 7.19 – 7.07 (comp, 4H), 7.10 (t, J = 7.5 Hz, 2H), 4.27 (s, 2H), 3.64 – 3.59 (m, 2H), 3.55 (d, J = 2.3 Hz, 2H), 3.25 (t, J = 5.8 Hz, 2H), 3.03 (t, J = 5.7 Hz, 2H), 1.66 – 1.60 (m, 2H), 1.33 – 1.25 (m, 10H), 0.91 – 0.85 (m, 3H).; 13C NMR (101MHz, chloroform-d) δ 174.4, 171.1, 153.1, 134.4, 134.4, 131.7, 130.8, 129.1, 129.0, 127.8, 126.4, 126.3, 125.9, 122.7, 122.4, 119.2, 53.4, 52.8, 38.9, 33.8, 31.8, 29.2, 29.1 (X 2), 27.9, 26.9, 22.6, 14.1.; HRMS (ESI, m / z) for C28H34N2O2 [M]+: calculated value 430.2620, measured value 430.2635.

[0101] Example 14 6-(2-Methoxyethyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2n): yellow solid (27.0 mg, 65% yield); Rf 0.20 (petroleum ether / ethyl acetate = 5:1); column chromatographic eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) δ 7.68 (d, J = 2.3 Hz, 1H), 7.47 (dd, J = 7.8, 1.5 Hz, 1H), 7.37 – 7.35 (m, 1H), 7.34 – 7.28 (m, 2H), 7.22 (td, J = 7.3, 1.8 Hz, 1H), 7.07 (d, J = 8.3 Hz, 1H), 6.97 – 6.92 (m, 1H), 6.87 (d, J = 7.6 Hz, 1H), 3.91 (d, J = 6.8 Hz, 1H), 3.88 – 3.78 (m, 2H), 3.75 – 3.68 (m, 1H), 3.62 – 3.51 (m, 4H), 3.33 (s, 3H), 3.17 (ddd, J = 13.5, 8.9, 4.0 Hz, 2H), 3.11 – 3.03 (m, 1H).13C NMR (101 MHz, chloroform-d) δ 172.1, 169.82, 149.9, 136.7, 135.0, 134.7, 133.4, 131.4, 129.1,127.9 (X 2), 127.7, 126.2, 126.0, 121.2, 119.6, 118.1, 68.7, 60.7, 58.5,53.5, 48.4, 37.7, 28.5. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-(2-methoxyethyl)pyrrolidine-2,5-dione (1n): yellow gel (260.0 mg, 53% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 7.99 (t, J = 2.2 Hz, 1H), 7.44 (dd, J = 7.7, 1.3 Hz, 1H), 7.41 – 7.35 (m, 1H), 7.19 –7.16 (comp, 4H), 7.10 (t, J = 7.5 Hz, 2H), 4.26 (s, 2H), 3.85 (t, J = 5.7 Hz, 2H), 3.64 (t, J = 5.7 Hz, 2H), 3.57 (d, J = 2.3 Hz, 2H), 3.37 (s, 3H), 3.24(t, J = 5.8 Hz, 2H), 3.03 (t, J = 5.7 Hz, 2H).; 13C NMR (101 MHz, chloroform-d) δ174.3, 171.0, 153.1, 134.3, 131.9, 130.8 (X 2), 129.0, 128.9, 127.6, 126.34,126.26, 125.9, 122.5, 122.4, 119.2, 68.7, 58.5, 53.4, 52.8, 37.9, 33.8, 29.1. Example 15 Ethyl 3-(5,7-dioxo-4c,5,14,15-tetrahydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-azirro[2,1-a]isoquinoline-6(7H)-yl)propionate (2o): yellow solid (26.2 mg, 63% yield); Rf 0.20 (petroleum ether / ethyl acetate = 5:1); column chromatographic eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) δ 7.68 (d, J = 2.3 Hz, 1H), 7.47 (dd, J = 7.8, 1.5 Hz, 1H), 7.37 – 7.35 (m, 1H), 7.34 – 7.28 (comp, 2H), 7.22 (td, J = 7.3, 1.8 Hz, 1H), 7.07 (d, J = 8.3Hz, 1H), 6.97 – 6.92 (m, 1H), 6.87 (d, J = 7.6 Hz, 2H), 4.15 – 4.09 (m, 2H), 3.92 – 3.79 (m, 4H), (d, J = 6.8 Hz, 1H), 3.88 – 3.78 (m, 1H), 3.62 – 3.51(m, 1H), 3.52 (dd, J = 6.8, 2.4 Hz), 3.17 (ddd, J = 13.5, 8.9, 4.0 Hz, 1H), 3.09 – 3.03 (m, 1H).13C NMR (101 MHz, chloroform-d) δ 171.8, 170.6, 169.5, 149.9, 136.7, 133.4, 131.5, 129.2, 127.9, 127.6, 126.0, 125.9, 121.1, 119.6, 117.9, 60.7, 60.6, 53.6, 48.3, 34.4, 32.2, 28.4, 14.1. Ethyl (E)-3-(3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-2,5-dioxopyrrolidine-1-yl)propionate (1o): yellow gel (260.0 mg, 50% yield); Rf 0.30 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 7.99 (d, J = 1.9 Hz, 1H), 7.45 – 7.35 (comp, 2H), 7.20 – 7.16 (m, 4H), 7.10 (t, J = 7.4 Hz, 2H), 4.26 (s, 2H), 4.18 – 4.11 (m, 2H), 3.94 (t, J = 7.3 Hz, 2H), 3.56 (d, J = 1.8 Hz, 2H), 3.24 (t, J = 5.7 Hz, 2H), 3.03 (t, J = 5.6 Hz, 2H), 2.69 (t, J = 7.3 Hz, 2H), 1.28 – 1.23 (m, 3H).; 13C NMR (101 MHz, chloroform-d) δ173.9, 170.7, 170.6, 153.1, 134.3, 132.1, 130.9, 129.0, 129.0, 127.6, 126.4,126.3, 125.9 (X 2), 122.4, 122.3, 119.2, 60.8, 53.4, 52.8, 34.5, 33.7, 32.3, 29.1, 14.1. Example 16 10-Chloro-6-ethyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-zircono[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2p): yellow solid (26.1 mg, 69% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) δ 7.55 (d, J = 2.3 Hz, 1H), 7.43 (d, J = 2.6 Hz, 1H), 7.36 – 7.27 (comp, 3H), 7.25 (d, J = 1.4 Hz, 1H), 6.99 (d, J = 8.9) Hz, 1H), 6.87 (d, J = 7.5 Hz, 1H), 3.89 (d, J =6.9 Hz, 1H), 3.78 (td, J = 10.6, 4.3 Hz, 1H), 3.65 – 3.51 (m, 4H), 3.21 –3.13 (m, 1H), 3.10 – 3.00 (m, 1H), 1.17 (t, J = 7.2 Hz, 3H).13C NMR (101 MHz, chloroform-d) δ 171.6, 169.4, 148.4, 135.1, 134.9, 133.2, 132.9, 131.0, 129.1,128.0, 127.8, 127.7, 126.2, 124.3, 122.4, 119.3, 60.5, 53.7, 48.5, 33.6, 28.3, 13.2. (E)-3-(5-chloro-2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-ethylpyrrolidine-2,5-dione (1p): off-white solid (270.0 mg, 79% yield); Rf 0.20 (petroleum ether / ethyl acetate = 20:1); column chromatography eluent, petroleum ether / EtOAc = 20:1; mp 128-130℃; single diastereomer; 1H NMR (400 MHz, chloroform-d)) δ 7.89 (t, J = 2.3 Hz, 1H), 7.38 (d, J = 2.4 Hz, 1H), 7.32 (dd, J = 8.6, 2.5 Hz, 1H), 7.19 (td, J = 6.6, 5.9, 2.8 Hz, 3H), 7.10 (dd, J = 6.9, 4.4 Hz, 2H), 4.24 (s, 2H), 3.70 (q, J = 7.2 Hz, 2H), 3.55 (d, J = 2.4 Hz, 2H), 3.23(t, J = 5.8 Hz, 2H), 3.01 (t, J = 5.7 Hz, 2H), 1.25 (t, J = 7.2 Hz, 3H).; 13CNMR (101 MHz, chloroform-d) δ 173.8, 170.6, 151.5, 134.2, 133.9, 130.4, 130.3,129.2, 129.1, 128.6, 127.7, 126.5, 126.3, 126.0, 124.1, 120.6, 53.4, 52.7, 33.9, 33.7, 29.0, 13.2.; HRMS (ESI, m / z) for C22H21ClN2O4 [M+H]+: calculated value 381.1370, measured value 381.1362.

[0102] Example 17 10-Chloro-6-phenyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-zircono[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2q): yellow solid (26.1 mg, 59% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:1); column chromatographic eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) δ 7.69 (d, J = 2.3 Hz, 1H), 7.48 (d, J = 2.5 Hz, 1H), 7.45 – 7.41 (comp, 2H), 7.37 – 7.29 (comp, 6H), 7.24 (td, J = 7.5, 2.3 Hz, 1H), 7.02 (d, J = 9.0 Hz, 1H), 6.95 (d, J = 7.6 Hz, 1H), 4.00 (d, J = 6.7 Hz, 1H), 3.85 – 3.78 (m, 1H), 3.73 (dd,J = 6.7, 2.3 Hz, 1H), 3.66 – 3.58 (m, 1H), 3.24 – 3.17 (m, 1H), 3.07 (dt, J =15.6, 4.6 Hz, 1H).13C NMR (101 MHz, chloroform-d) δ 170.7, 168.6, 148.5, 135.2,134.9, 134.2, 133.0, 131.8, 131.3, 129.1, 129.0 (X 2), 128.3, 128.1, 127.7, 127.0, 126.4, 126.3 (X 2), 124.3, 122.4, 119.3, 60.8, 53.8, 48.6, 28.2.HRMS(ESI, m / z) for C26H19ClN2O2 [M]+ is calculated to be 426.1135, and the measured value is 426.1137.

[0103] (E)-3-(5-chloro-2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-phenylpyrrolidine-2,5-dione (1q): yellow solid (800.0 mg, 99% yield); Rf 0.20 (petroleum ether / ethyl acetate = 20:1); column chromatography eluent, petroleum ether / EtOAc = 20:1; mp 140–142 °C; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 8.03 (t, J = 2.4 Hz, 1H), 7.53 – 7.48 (comp, 2H), 7.45 – 7.39 (m, 4H), 7.36 (dd, J = 8.7, 2.5 Hz, 2H), 7.21 – 7.13 (comp, 4H), 7.11 (d, J = 4.9 Hz, 1H), 4.29 (s, 2H), 3.76 (d, J = 2.4 Hz, 2H), 3.28 (t, J = 5.8 Hz, 2H), 3.03 (t, J= 5.8 Hz, 2H).; 13C NMR (101 MHz, chloroform-d) δ 172.9, 169.7, 151.6, 134.1,133.9, 131.9, 131.5, 130.6, 129.0 (X 3), 128.9, 128.6, 128.5, 127.6, 126.5,126.3 (X 3), 126.0, 123.3, 120.5, 53.3, 52.9, 33.8, 29.1.; HRMS (ESI, m / z) for C26H21ClN2O2 [M+H]+: calculated value 429.1370, measured value 429.1360.

[0104] Example 18 6-Benzyl-11-chloro-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-zircono[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2r): yellow solid (19.8 mg, 45% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:1); column chromatographic eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) δ 7.61 (d, J = 2.3 Hz, 1H), 7.37 (dd, J = 7.9, 1.8 Hz, 3H), 7.33 (dd, J = 7.3, 1.1 Hz, 1H), 7.31 – 7.26 (comp, 4H), 7.25 – 7.20 (comp, 2H), 7.00 (d, J = 1.9 Hz, 1H), 6.90 (dd, J = 8.4, 2.0 Hz, 1H), 6.80 (d, J = 7.4 Hz, 1H), 4.74 – 4.62(m, 2H), 3.92 (d, J = 6.9 Hz, 1H), 3.74 (td, J = 10.8, 4.1 Hz, 1H), 3.60 (dt,J = 11.0, 4.6 Hz, 1H), 3.54 (dd, J = 6.9, 2.3 Hz, 1H), 3.16 (ddd, J = 15.2,10.5, 4.5 Hz, 1H), 3.02 (dt, J = 15.5, 4.3 Hz, 1H). 13C NMR (101 MHz, chloroform-d) δ 171.3, 169.3, 150.4, 137.6, 137.4, 136.1, 135.0, 133.8, 133.1, 129.0 (X 2), 128.9, 128.6 (X 2), 128.1, 127.8, 127.6, 126.4, 126.3, 119.9, 119.7, 117.4, 60.7, 54.0, 48.4, 42.2, 28.1. HRMS (ESI, m / z) for C27H21ClN2O2 [M]+ Calculated value: 440.1292; measured value: 440.1284.

[0105] (E)-1-Benzyl-3-(4-chloro-2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)pyrrolidine-2,5-dione (1r): yellow solid (248.0 mg, 56% yield); Rf 0.30 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 167–169 °C; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 7.87 (t, J = 2.0 Hz, 1H), 7.48 – 7.41 (comp, 2H), 7.35 – 7.27 (comp, 4H), 7.21 – 7.15 (comp, 3H), 7.12 (d, J = 1.9 Hz, 1H), 7.10 – 7.02 (comp, 2H),4.78 (s, 2H), 4.22 (s, 2H), 3.52 (d, J = 2.3 Hz, 2H), 3.22 (t, J = 5.8 Hz,2H), 3.03 (t, J = 5.6 Hz, 2H); 13C NMR (101 MHz, chloroform-d) δ 173.6, 170.5,154.1, 136.7, 135.9, 134.1, 133.7, 131.0, 129.9, 129.1, 129.0, 128.7, 128.0,126.6, 126.3, 126.1, 125.9, 122.9, 122.5, 119.6, 53.3, 52.7, 42.5, 33.8, 29.2; HRMS (EI, m / z) for C27H23ClN2O2 [M]+: calculated value 442.1448, measured value 442.1446.

[0106] Example 19 3-Methyl-6-phenyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2s): yellow solid (21.1 mg, 52% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; 1H NMR (400 MHz, chloroform-d) δ 7.80 (d, J = 2.3 Hz, 1H), 7.51 (dd, J = 7.8, 1.4 Hz, 1H), 7.48 – 7.42 (comp, 2H), 7.39 – 7.33 (comp, 4H), 7.18 (d, J = 2.3 Hz, 1 ...comp, 2H), 7.18 (comp, 2H), 7.18 (comp, 2H), 7.18 (comp, 2H), 7.18 (comp, 2H), 7.18 (comp, 2H), 7.18 (comp, 2H), 7.18 (comp, 7.7 Hz, 1H), 7.13 – 7.05 (comp, 2H), 6.99 – 6.93 (m, 1H), 6.76 (s, 1H), 3.98 (d, J = 6.7 Hz, 1H), 3.83 (td, J =10.6, 4.2 Hz, 1H), 3.72 (dd, J = 6.7, 2.3 Hz, 1H), 3.67 – 3.60 (m, 1H), 3.17 (ddd, J = 14.7, 10.2, 4.3 Hz, 1H), 3.03 (dt, J = 15.4, 4.6 Hz, 1H), 2.30 (s,3H).13C NMR (101 MHz, chloroform-d) δ 171.0, 169.1, 150.2, 136.9, 135.8 (X 2), 133.4, 132.2, 132.2, 131.7, 129.7, 129.0 (X 2), 128.8, 128.3, 127.5, 126.4, 125.8 (X 2), 121.2, 119.7, 117.8, 61.1, 54.1, 48.7, 28.0, 21.4.HRMS (ESI, m / z) Calculated value for C27H22N2O2 [M]+ is 406.1618, measured value is 406.1674.

[0107] (E)-3-(2-(7-methyl-3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-phenylpyrrolidine-2,5-dione (1s): pale green solid (343.0 mg, 76%); Rf 0.10 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 114–116 °C; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 8.11 (d, J = 2.1 Hz, 1H), 7.53 – 7.47 (comp, 3H), 7.44 – 7.38 (comp, 4H), 7.19 (d, J = 8.1 Hz, 1H), 7.13 (t, J = 7.5 Hz, 1H), 7.07 – 6.99 (comp, 2H), 6.92 (s, 1H), 4.25 (s, 2H), 3.76 (d, J = 2.3 Hz, 2H), 3.26 (t, J = 5.8 Hz, 2H), 2.99 (t, J = 5.6 Hz, 2H), 2.32 (s, 3H).; 13C NMR (101 MHz, chloroform-d) δ 173.3, 170.1, 153.3, 135.4, 134.1, 133.1, 132.1, 131.3, 131.0, 129.1 (X 3), 128.9, 128.4, 127.5, 127.3, 126.8, 126.4 (X 2), 122.4, 122.0, 119.3, 53.4,53.2, 34.1, 28.8, 21.0.; HRMS (EI, m / z) for C27H24N2O2 [M]+: calculated value 408.1838, measured value 408.1825.

[0108] Example 20 2,3-Dimethoxy-6-phenyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]azabenzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2t): yellow solid (26.7 mg, 59% yield); Rf 0.10 (petroleum ether / ethyl acetate = 5:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) δ 7.80 (d, J = 2.2 Hz, 1H), 7.53 – 7.49 (m, 1H), 7.45 (t, J = 7.6 Hz, 2H), 7.41– 7.33 (m, 4H), 7.11 (d, J = 8.4) Hz, 1H), 6.97 (t, J = 7.4 Hz, 1H), 6.78 (s,1H), 6.42 (s, 1H), 3.95 (d, J = 6.8 Hz, 2H), 3.90 (s, 3H), 3.88 – 3.83 (m,1H), 3.76 (s, 3H), 3.67 (dd, J = 6.6, 2.2 Hz, 1H), 3.61 – 3.53 (m, 1H), 3.12(ddd, J = 13.2, 8.8, 4.3 Hz, 1H), 3.03 (dt, J = 15.5, 5.1 Hz, 1H).13C NMR (101 MHz, chloroform-d) δ 172.0, 169.8, 149.9, 136.7 (X 2), 135.1, 134.5, 133.5, 131.4, 129.1 (X 2), 127.9, 127.6 (X 2), 126.3, 126.1 (X 2), 121.2, 119.6 (X 2), 117.8 (X 2), 60.6, 53.8, 48.3, 33.5, 28.4, 13.3.HRMS (ESI, m / z) Calculated value for C28H24N2O4 [M+H]+ is 453.1814, measured value is 453.1806.

[0109] (E)-3-(2-(6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-phenylpyrrolidine-2,5-dione (1t): yellow solid (376.8 mg, 83% yield); Rf 0.30 (petroleum ether / ethyl acetate = 5:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; mp 142–145℃; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 8.10 (t, J = 2.1 Hz, 1H), 7.52 – 7.48 (comp, 3H), 7.43 – 7.34 (comp, 4H), 7.17 (app d, J = 8.0 Hz, 1H), 7.15 – 7.11 (m, 1H), 6.63 (s, 1H), 6.59(s, 1H), 4.21 (s, 2H), 3.87 (d, J = 5.6 Hz, 1H), 3.85 (d, J = 2.3 Hz, 6H), 3.75 (d, J = 1.9 Hz, 2H), 3.25 (t, J = 5.8 Hz, 2H), 2.94 (t, J = 5.6 Hz, 2H);13C NMR (101 MHz, chloroform-d) δ 173.3, 170.1, 153.3, 147.7, 147.5, 133.1, 132.1,131.0, 129.1, 129.1, 128.4, 127.5, 126.6, 126.4, 126.1, 122.3, 122.0, 119.2,111.7, 109.2, 56.0, 55.9, 53.1, 52.9, 34.0, 28.8; HRMS (ESI, m / z) for C28H26N2O4 [M]+: calculated value 454.1893, measured value 454.1846.

[0110] Example 21 2,3-Dimethoxy-6-methyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]azabenzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2u): yellow solid (30.0 mg, 77% yield); Rf 0.10 (petroleum ether / ethyl acetate = 5:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; 1H NMR (400 MHz, chloroform-d) δ 7.67 (d, J = 2.3 Hz, 1H), 7.47 (dd, J = 7.8, 1.6 Hz, 1H), 7.35 (ddd, J = 8.6, 7.1, 1.7 Hz, 1H), 7.07 (d, J = 8.3). Hz, 1H), 6.94 (t, J = 6.9 Hz, 1H), 6.77 (s, 1H), 6.34 (s, 1H), 3.92 (s, 3H), 3.87 – 3.80 (m, 2H), 3.78 (s, 3H), 3.52 (ddd, J = 13.3, 6.3, 3.3 Hz, 2H), 3.10 – 2.99 (m, 5H). 13C NMR (101 MHz, chloroform-d) δ 172.2, 170.1, 150.0, 148.6, 147.1, 136.6, 134.4, 131.4, 127.3, 126.3, 125.1, 121.3, 119.7, 118.4, 112.6, 110.7, 60.4, 56.1, 55.9, 53.4, 48.5, 28.3, 24.7.HRMS (ESI, m / z) for C23H22N2O4 [M]+: calculated value 390.1580, measured value 390.1579.

[0111] (E)-3-(2-(6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-methylpyrrolidine-2,5-dione (1u): yellow solid (321.0 mg, 68% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:3); column chromatography eluent, petroleum ether / EtOAc = 10:3; mp 98–100 °C; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 7.99 (t, J = 2.2 Hz, 1H), 7.43 (dd, J = 7.7, 1.3 Hz, 1H), 7.40 – 7.34 (m, 1H), 7.16 (d, J = 8.1 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 6.66 (s, 1H), 6.59 (s, 1H), 4.20 (s, 2H), 3.87 (d, J = 1.9 Hz, 6H), 3.57 (d, J = 2.3 Hz, 2H), 3.22 (t, J = 5.8 Hz, 2H), 3.13 (s, 2H), 2.93 (t, J = 5.6 Hz, 2H).; 13CNMR (101 MHz, chloroform-d) δ 174.9, 171.1, 153.1, 147.6, 147.4, 146.9, 143.9,143.8, 132.0, 130.8, 129.0, 127.5, 126.3, 126.1, 122.6, 123.1, 122.8, 122.6,122.4, 119.2, 111.6, 109.1, 56.0, 55.9, 52.4, 52.1, 46.7, 33.8, 28.5, 25.3; Example 22 2,3-Dimethoxy-6-(3,4,5-trimethoxyphenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2v): brown solid (19.0 mg, 50% yield); Rf 0.10 (petroleum ether / ethyl acetate = 2:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; mp 158–160 °C; 1H NMR (400 MHz, chloroform-d) δ 7.79 (d, J = 2.0 Hz, 1H), 7.51 (d, J = 7.4 Hz, 1H), 7.38 (app t, J = 7.1 Hz, 1H), 7.11 (d, J = 8.4 Hz, 1H), 6.97 (app t, J =7.4 Hz, 1H), 6.79 (s, 1H), 6.57 (app s, 2H), 6.42 (s, 1H), 3.96 (d, J = 6.6Hz, 1H), 3.90 (s, 3H), 3.84 (d, J = 10.1 Hz, 10H), 3.76 (s, 3H), 3.68 (dd, J= 6.4, 2.0 Hz, 1H), 3.60 – 3.55 (m, 1H), 3.16 – 3.00 (m, 2H).13C NMR (101MHz, Chloroform-d) δ 171.2, 169.1, 153.3 (X 2), 150.2, 148.7, 147.2, 136.8, 135.7,131.7, 127.6, 127.3, 125.4, 125.1, 121.3, 119.8, 118.3, 112.5, 110.7, 104.0(X 3), 60.8, 60.7, 56.1, 56.0, 55.9, 53.6, 48.6, 29.7, 28.2.HRMS (EI, m / z) For C31H30N2O7 [M]+, the calculated value is 542.2057, and the measured value is 542.2067.

[0112] ( E )-3-(2-(6,7-dimethoxy-3,4-dihydroisoquinoline-2(1 H)-(3,4,5-trimethoxyphenyl)pyrrolidine-2,5-dione (1v): brown solid (150.0 mg, 55% yield); Rf 0.30 (petroleum ether / ethyl acetate = 2:1); column chromatography eluent, petroleum ether / EtOAc = 2:1; mp 128 – 130 °C; diastereomer ratio 100:12; non-separable diastereomer mixture; 1H NMR (400 MHz, chloroform-d) δ 8.13 (t, J = 2.1 Hz, 1H), 7.49 (dd, J = 7.6, 1.2 Hz, 1H), 7.43 – 7.39 (m, 1H), 7.21 (d, J = 7.6 Hz, 1H), 7.15 (t, J = 7.5 Hz, 1H). Hz, 1H), 6.64 – 6.60 (comp, 4H), 4.26 (s, 1H), 3.87 – 3.86 (m, 15H), 3.75 (d, J = 2.3 Hz, 1H), 3.29 (t, J = 5.7 Hz, 1H), 2.95 (t, J = 5.2 Hz, 2H).; 13C NMR (101 MHz, chloroform-d) δ 173.4, 170.3, 153.5,153.3, 147.7, 147.5, 138.1, 133.3, 132.1, 132.0, 131.9, 131.1, 129.1, 128.5,128.4, 127.6, 127.4, 126.4, 126.1, 122.4, 121.8, 119.3, 111.7, 109.2, 104.2, 60.8, 56.2, 55.0, 55.9, 53.0, 53.0, 34.0, 28.7.; HRMS (EI, m / z) for C31H32N2O7 [M]+: calculated value 544.2210, measured value 544.2215.

[0113] Example 23 6-(4-Phenylacetyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2w): yellow gel (23.0 mg, 51% yield); Rf 0.10 (petroleum ether / ethyl acetate = 100:15); column chromatographic eluent, petroleum ether / EtOAc = 100:15; 1H NMR (400 MHz, chloroform-d) δ 7.66 (d, J = 2.2 Hz, 1H), 7.47 (dd, J = 7.8, 1.4 Hz, 1H), 7.37 – 7.32 (comp, 2H), 7.30 (d, J = 2.9 Hz, 1H), 7.30 – 7.29 (m, 1H), 7.28 – 7.24 (m, 1H), 7.20- 7.14 (comp, 5H), 6.05 (d, J = 8.4 Hz, 1H), 6.96 – 6.92 (m, 1H), 6.80 (d, J= 7.6 Hz, 1H), 3.90 (d, J = 6.8 Hz, 1H), 3.82 (td, J = 10.5, 4.3 Hz, 1H), 3.63 – 3.51 (m, 4H), 3.21 – 3.13 (m, 1H), 3.05 (dt, J = 15.5, 4.7 Hz, 1H),2.61 (t, J = 7.1 Hz, 2H), 1.65 – 1.57 (m, 5H). 13C NMR (101 MHz, chloroform-d) δ 172.1, 169.9, 149.9, 142.0, 136.7, 135.1, 134.6, 133.5, 131.4, 129.0, 128.4 (X 2), 128.3 (X 2), 127.9, 127.6, 126.2, 126.1, 125.8, 121.2, 119.6, 117.9, 60.7, 53.7, 48.3, 38.4, 35.4, 28.7, 28.4, 27.5. HRMS (ESI, m / z) The calculated value for C30H28N2O2 [M]+ is 448.2151, and the measured value is 448.2155.

[0114] (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-(4-phenylbutyl)pyrrolidine-2,5-dione (1w): yellow gel (334.0 mg, 59% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; diastereomer ratio 100:10; non-separable diastereomer mixture; 1H NMR (400 MHz, chloroform-d) δ 8.01 (t, J = 2.2 Hz, 1H), 7.45 (dd, J = 7.7, 1.3 Hz, 1H), 7.42 – 7.37 (m, 1H), 7.32 – 7.28 (comp, 2.6H), 7.23 – 7.17 (comp, 8H),7.14 – 7.10 (comp, 2.45H), 4.28 (s, 2H), 4.22 (s, 0.15H), 3.68 (t, J = 6.9Hz, 2H), 3.55 (d, J = 2.3 Hz, 2H), 3.44 (d, J = 1.9 Hz, 0.20H), 3.26 (t, J =5.8 Hz, 2H), 3.05 (t, J = 5.7 Hz, 2H), 2.99 (t, J = 5.8 Hz, 0.21H), 2.69 (t,J = 7.2 Hz, 2.55H), 1.71 (tqd, J = 15.5, 7.6, 3.8 Hz, 5H); 13C NMR (101 MHz, chloroform-d) δ 174.3, 171.0, 153.1, 141.9, 134.3, 134.3, 131.7, 130.7, 129.0, 128.9, 128.9, 128.3 (X 2), 128.2, 127.6, 126.3, 126.2, 125.8, 125.7, 122.6, 122.3, 119.1, 53.3, 52.8, 38.5, 35.3, 33.7, 29.1, 28.6, 27.4; HRMS (EI, m / z) for C30H30N2O2 [M]+ Calculated value 450.2307, measured value 450.2305.

[0115] Example 24 6-Phenylacetyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2x): yellow gel (21.0 mg, 50% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; 1 H NMR (400 MHz, chloroform-d) δ 7.66 (d, J =2.2 Hz, 1H), 7.48 (dd, J = 7.8, 1.5 Hz, 1H), 7.37 – 7.34 (m, 1H), 7.33 – 7.30(comp, 2H), 7.29 – 7.28 (m, 1H), 7.24 – 7.21 (comp, 3H), 7.19 – 7.14 (comp,2H), 7.05 (d, J = 8.4 Hz, 1H), 6.96 – 6.93 (m, 1H), 6.56 (d, J = 7.6 Hz, 1H), 3.90 – 3.84 (m, 1H), 3.83 – 3.79 (m, 2H), 3.78 – 3.73 (m, 1H), 3.78 – 3.73(m, 1H), 3.61 – 3.55 (m, 1H), 3.46 (dd, J = 6.8, 2.2 Hz, 1H), 3.18 – 3.11 (m,1H), 3.07 – 3.01 (m, 1H), 2.98 – 2.88 (m, 2H). 13 C10 NMR (101 MHz, chloroform-d) δ 171.7, 169.8, 149.9, 138.0, 136.7, 135.0, 134.5, 133.3, 131.4, 129.2, 129.0 (x 2), 128.5 (x 2), 127.8, 127.6, 126.6, 126.2, 126.0, 121.2, 119.6, 118.0, 60.6, 53.5, 48.4, 39.7, 33.6, 28.5. HRMS (EI, m / z) for C28H24N2O2 [M]+ Calculated value: 420.1838; measured value: 420.1831.

[0116] (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-phenethylpyrrolidine-2,5-dione (1x): yellow solid (380.0 mg, 70% yield); Rf 0.50 (petroleum ether / ethyl acetate = 10:4); column chromatography eluent, petroleum ether / EtOAc = 10:4; mp 120 – 122℃; diastereomer ratio 100:14; non-separable diastereomer mixture; 1 H NMR (400 MHz, chloroform-d) δ 7.99 (app s, 1H), 7.45 – 7.38 (comp, 2.5H), 7.34 – 7.18 (comp, 11H), 7.12 (t, J = 7.0 Hz, 2.6H), 4.28 (s, 2H), 4.23 (s, 0.27H), 3.92 – 3.85 (m, 2.4H), 3.52 (d, J = 2.1 Hz, 2H), 3.41 (d, J= 1.5 Hz, 0.29H), 3.25 (t, J = 5.8 Hz, 2.37H), 3.10 – 2.98 (m, 5H).; 13 C NMR (101 MHz, chloroform-d) δ 174.0, 173.6, 170.7, 168.2, 153.0, 151.9, 137.8, 137.2, 134.6, 134.2, 134.1, 131.7, 131.6, 129.0, 128.9, 128.7, 128.4, 127.5, 127.4, 126.5, 126.4, 126.3, 126.2, 125.9, 125.8, 122.4, 122.3, 121.8, 121.6, 119.1, 118.0, 54.1, 53.3, 52.7, 51.8, 39.9, 39.7, 35.9, 33.6, 29.1.; HRMS (EI, m / z) calculated value for C28H26N2O2 [M]+ as 422.1994, measured value as 422.1988.

[0117] Example 25 6-(2-(thiophen-2-yl)ethyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2y): yellow gel (20.0 mg, 47% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; 1 H NMR(400 MHz, chloroform-d)δ δ 7.66 (d, J = 2.3 Hz, 1H), 7.47 (dd, J = 7.8, 1.5 Hz, 1H), 7.37 – 7.33(comp, 2H), 7.32 – 7.29 (m, 1H), 7.21 – 7.17 (comp, 2H), 7.14 (dd, J = 5.1,1.1 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 6.97 – 6.90 (m, 2H), 6.83 (dd, J =3.2, 0.8 Hz, 1H), 6.69 (d, J = 7.5 Hz, 1H), 3.87 – 3.86 (m, 1H), 3.84 – 3.74(m, 3H), 3.62 – 3.56 (m, 1H), 3.50 (dd, J = 6.8, 2.2 Hz, 1H), 3.22 – 3.12 (m,4H), 3.05 (dt, J = 15.5, 4.8 Hz, 1H). 13 C NMR (101 MHz, chloroform-d) δ 171.8, 169.7, 153.2, 139.9, 136.7, 135.1, 134.8, 133.4, 131.5, 129.2, 127.9, 127.6, 127.0 (X 2), 126.0, 125.7, 124.1, 121.2, 119.7, 117.9, 60.6, 53.6, 48.4, 39.8, 28.5, 27.5. HRMS (EI, m / z) Calculated value for C26H22N2O2S [M]+: 426.1402, measured value: 426.1393.

[0118] (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-(2-(thiophen-2-yl)ethyl)pyrrolidine-2,5-dione (1y): yellow gel (355.0 mg, 59% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:4); column chromatography eluent, petroleum ether / EtOAc = 10:4; diastereomer ratio 100:25; non-separable diastereomer mixture; 1 H NMR (400 MHz, chloroform-d) δ 7.99 (app s, 1H), 7.94 (d, J = 7.6 Hz, 0.13H), 7.44 – 7.37 (comp, 2.6H), 7.20 – 7.09 (comp, 9.2H), 6.96 – 6.92 (m,1.5H), 6.89 (d, J = 3.0 Hz, 1.3H), 4.27 (s, 1H), 4.22 (s, 0.2H), 3.95 – 3.89(m, 2H), 3.87 – 3.83 (m, 0.5H), 3.54 (d, J = 2.3 Hz, 1H), 3.43 (d, J = 1.8Hz, 0.3H), 3.29 – 3.18 (m, 5H), 3.04 (t, J = 5.6 Hz, 2H), 2.99 (d, J = 5.3Hz, 0.5H).; 13 C NMR (101 MHz, chloroform-d) δ 174.0, 170.7, 168.2, 153.1, 152.0, 139.8, 137.5, 134.6, 134.28, 133.8, 132.0, 131.6, 130.8, 130.7, 129.0, 128.9, 127.5, 127.5, 126.9, 126.3, 126.3, 125.9, 125.5, 124.0, 122.4, 122.3, 121.9, 121.6, 119.1, 118.1, 54.2, 53.4, 52.7, 51.8, 40.0, 39.8, 35.9, 33.7, 29.5, 29.2, 27.6, 27.5.; HRMS (EI, m / z) calculated value for C26H24N2O2S [M]+ as 428.1558, measured value as 428.1550.

[0119] Example 26 6-(3-Methoxyphenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2z): yellow solid (30.9 mg, 69% yield); Rf 0.20 (petroleum ether / ethyl acetate = 5:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; mp 178-180℃; 1 H NMR(400 MHz, chloroform-d) δ 7.80 (d, J = 2.3 Hz, 1H), 7.52 (dd, J = 7.8, 1.5 Hz, 1H), 7.40 – 7.29(comp, 4H), 7.23 – 7.19 (m, J = 7.7, 3.2 Hz, 1H), 7.09 (d, J = 8.4 Hz, 1H), 6.99 – 6.88 (comp, 5H), 3.89 – 3.83 (m, 1H), 3.79 (s, 3H), 3.76 – 3.71 (m,1H), 3.65 (dd, J = 10.5, 5.6 Hz, 0H), 3.30 – 3.17 (m, 1H), 3.08 (dt, J =15.5, 4.7 Hz, 1H). 13 C10 NMR (101 MHz, chloroform-d) δ 170.9, 168.9, 159.9, 150.1, 136.8, 135.7, 135.0, 133.4, 133.0, 131.6, 129.6, 129.2, 127.9, 127.6, 126.3, 125.6, 121.2, 119.7, 118.7, 117.9, 114.3, 112.2, 60.9, 55.4, 53.8, 48.4, 28.4. HRMS (EI, m / z) for C27H22N2O3 [M]+ Calculated value: 422.1630; measured value: 422.1622.

[0120] (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-(3-methoxyphenyl)pyrrolidine-2,5-dione (1z): yellow gel (280.0 mg, 73% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; diastereomer ratio 100:7; non-separable diastereomer mixture; 1H NMR (400 MHz, chloroform-d) δ 8.11 (t, J = 2.3 Hz, 1H), 7.50 (dd, J = 7.8, 1.3Hz, 1H), 7.44 – 7.37 (comp, 2.3 H), 7.22 – 7.15 (comp, 5H), 7.14 – 7.09(comp, 2H), 7.01 – 6.99 (m, 1H), 6.97 – 6.94 (comp, 2H), 4.29 (s, 2H), 4.24(d, J = 3.6 Hz, 0.18H), 3.83 (s, 2H), 3.82 (s, 0.21 H), 3.75 (d, J = 2.4 Hz,2H), 3.73 (s, 0.11 H), 3.28 (t, J = 5.8 Hz, 2H), 3.05 (t, J = 5.7 Hz, 2H).; 13 CNMR (101 MHz, chloroform-d) δ 173.2, 170.0, 160.0, 153.3, 134.4, 134.3, 133.1 (X 2), 131.0, 129.8, 129.1 (X 2), 127.5, 126.4, 126.3, 125.9, 122.4, 122.0, 119.2, 118.7, 114.5, 112.2, 55.4, 53.4, 53.0, 34.0, 29.2; HRMS (ESI, m / z) for C27H24N2O3 [M+H]+ Calculated value: 424.1787; Measured value: 424.1805.

[0121] Example 27 6-Phenylon-14,15-dihydro-4bH-pyrido[3',2':6,7]pyrrolo[3',4':3,4]azazo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2za): yellow solid (30.0 mg, 76% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:3); column chromatography eluent, petroleum ether / EtOAc = 5:1; mp 204-206℃; 1H NMR(400 MHz, chloroform-d) δ 8.34 (dd, J = 4.6, 1.8 Hz, 1H), 7.77 (dd, J = 7.6, 1.7 Hz, 1H), 7.70(d, J = 2.0 Hz, 1H), 7.46 – 7.42 (comp, 2H), 7.37 – 7.31 (comp, 5H), 7.24 –7.20 (m, 1H), 6.95 (d, J = 7.5 Hz, 1H), 6.87 (dd, J = 7.6, 4.6 Hz, 1H), 4.21– 4.14 (m, 2H), 3.96 (td, J = 11.9, 3.9 Hz, 1H), 3.71 (dd, J = 6.3, 2.2 Hz, 1H), 3.23 – 3.12 (m, 1H), 3.03 (dt, J = 15.5, 4.0 Hz, 1H). 13 C NMR (101 MHz, chloroform-d) δ 170.6, 168.6, 157.9, 150.1, 144.6, 136.0, 134.0, 132.6, 132.0, 129.0, 129.0 (X 2), 128.4, 128.3, 127.7, 126.7, 126.5, 126.4 (X 2), 114.9, 114.7, 61.3, 54.0, 46.4, 28.1. LCMS (EI, m / z) Calculated value for C25H19N3O2 [M]+ 393.00, measured value 393.00.

[0122] (E)-3-((2-(3,4-dihydroisoquinoline-2(1H)-yl)pyridin-3-yl)methylene)-1-phenylpyrrolidine-2,5-dione (1za): pale green solid (250.0 mg, 30% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:3); column chromatography eluent, petroleum ether / EtOAc = 10:3; mp 90 - 92℃; single diastereomer; 1H NMR (400 MHz, chloroform-d) δ 8.34 (dd, J = 4.8, 1.8 Hz, 1H), 7.85 (t, J = 2.3 Hz, 1H), 7.70 (dd,J = 7.6, 1.7 Hz, 1H), 7.53 – 7.49 (comp, 2H), 7.44 – 7.40 (comp, 3H), 7.21 –7.15 (comp, 4H), 6.97 – 6.94 (m, 1H), 4.59 (s, 2H), 3.69 (d, J = 2.4 Hz, 2H), 3.54 (t, J = 5.8 Hz, 2H), 3.11 (t, J = 5.7 Hz, 2H). 13 C NMR (101 MHz, chloroform-d) δ 172.8, 169.6, 161.4, 148.9, 137.2, 134.4, 134.3, 132.2, 131.9, 129.1 (X2), 128.9, 128.6, 126.6, 126.4, 126.3 (X2), 126.1, 122.9, 119.0, 116.2, 51.2, 50.5, 33.7, 29.5.; HRMS (EI, m / z) Calculated value for C25H21N3O2 [M]+ 395.1634, measured value 395.1627.

[0123] Example 28 6-(4-Chlorophenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2zb): yellow solid (26.1 mg, 70% yield); Rf 0.10 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 158-160℃; 1H NMR (400 MHz, chloroform-d) δ 7.81 (d, J = 2.0 Hz, 1H), 7.52 (dd, J = 7.8, 1.5 Hz, 1H), 7.41 – 7.36 (comp, 3H), 7.33 – 7.29 (comp, 4H), 7.22 (td, J = 6.9, 6.3, 2.5 Hz, 2H), 7.09(d, J = 8.4 Hz, 1H), 6.99 – 6.92 (comp, 2H), 4.02 (d, J = 6.4 Hz, 1H), 3.90 –3.83 (m, 1H), 3.72 (dd, J = 6.7, 2.3 Hz, 1H), 3.68 – 3.62 (m, 1H), 3.24 –3.17 (m, 1H), 3.08 (dt, J = 15.5, 4.7 Hz, 1H). 13 C NMR (101 MHz, chloroform-d) δ 170.9, 168.7, 150.2, 137.0, 136.2, 135.2, 133.9, 133.4, 131.9, 129.2 (X 3), 128.1, 127.8, 127.6 (X 2), 126.4, 125.2, 121.2, 119.9, 118.0, 61.0, 54.0, 48.5, 28.5. HRMS (EI, m / z) For C26H19ClN2O2 [M]+, the calculated value is 426.1135, and the measured value is 426.1137.

[0124] (E)-1-(4-chlorophenyl)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)pyrrolidine-2,5-dione (1zb): pale green solid (400.0 mg, 74% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:3); column chromatography eluent, petroleum ether / EtOAc = 5:1; mp 108-110℃; diastereomer ratio 10:1; non-separable diastereomer mixture; 1H NMR(400 MHz, chloroform-d) δ 8.12 (t, J = 2.2 Hz, 1H), 7.50 – 7.44(comp, 4H), 7.42 – 7.38 (comp, 3H), 7.22 – 7.20 (comp, 2H), 7.19 – 7.17(comp, 2.8 H), 7.13 (d, J = 8.2 Hz, 1.4 H), 4.29 (s, 2H), 4.24 (s, 0.2H), 3.75 (d, J = 2.0 Hz, 2H), 3.71 (s, 0.2 H), 3.27 (t, J = 5.8 Hz, 2H), 3.05 (t,J = 5.7 Hz, 2H). 13 C NMR (101 MHz, chloroform-d) δ 173.0, 169.8, 153.3, 134.3, 134.2, 134.1, 133.4, 131.2, 130.5, 129.7, 129.2, 129.0, 129.0, 127.6, 127.4 (X 2), 126.4, 126.3, 126.0, 122.4, 121.6, 119.3, 53.4, 53.0, 34.0, 29.2.; HRMS (EI, m / z) Calculated value for C26H21ClN2O2 [M]+ 428.1292, measured value 428.1297.

[0125] Example 29 11-Phenyl-1,2,3,12b-tetrahydrobenzo[f]dipyrrolo[1,2-a:3',4'-c]azapyridine-10,12(11H,12aH)-dione (2zc): yellow solid (22.0 mg, 67% yield); Rf 0.20 (petroleum ether / ethyl acetate = 20:1); column chromatography eluent, petroleum ether / EtOAc = 20:1; mp 178-180℃; 1H NMR(400 MHz, chloroform-d) δ 7.71(d, J = 2.2 Hz, 1H), 7.52 – 7.47 (comp, 1H), 7.42 – 7.37 (comp, 4H), 7.34 –7.30 (m, 1H), 6.85 – 6.81 (comp, 2H), 3.65 – 3.55 (m, 2H), 3.41 – 2.89 (m,3H), 2.35 – 1.94 (m, 4H). 13 C NMR (101 MHz, chloroform-d) δ 173.0, 169.2, 147.3, 136.7, 132.1, 131.7, 129.0 (X 2), 128.3, 126.5 (X 3), 123.9, 118.6, 117.7, 115.2, 59.4, 51.4, 51.1, 29.0, 22.9. HRMS (ESI, m / z) For C21H18N2O2 [M]+, the calculated value is 330.1368, and the measured value is 330.1371.

[0126] (E)-1-Phenylon-3-(2-(pyrrolidone-1-yl)benzyl)pyrrolidine-2,5-dione (1zc): off-white solid (252.0 mg, 76% yield); Rf 0.30 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 140–142 °C; single diastereomer; ¹H NMR (400 MHz, chloroform-d) δ 8.00 (t, J = 2.3 Hz, 1H), 7.51 – 7.46 (comp, 2H), 7.42 – 7.36 (comp, 3H), 7.34 – 7.25 (comp, 2H), 6.93 (d, J = 8.2 Hz, 1H), 6.90 – 6.84 (m, 1H), 3.46 (d, J = 2.4 Hz, 2H), 3.22 (t, J = 6.6 Hz, 4H), 1.99 – 1.89 (m, 4H); 13C NMR (101 MHz, chloroform-d) δ 173.6, 170.2, 149.9, 136.0, 132.1, 130.5, 129.8, 129.0 (X 2), 128.4, 126.5 (X 2), 122.7, 120.9, 118.7, 115.4, 52.4, 33.9, 25.6 (X 3).; HRMS (EI, m / z) for C21H20N2O2 [M]+ Calculated value: 332.1525; measured value: 332.1519.

[0127] Example 30 11-(p-Tolyl)-1,2,3,12b-tetrahydrobenzo[f]dipyrrolo[1,2-a:3',4'-c]azapyridine-10,12(11H,12aH)-dione (2zd): yellow solid (16.0 mg, 47% yield); Rf 0.30 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 198-200℃; 1¹H NMR (400 MHz, chloroform-d) δ 7.68 (d, J = 2.3 Hz), 7.40 – 7.38 (m, 1H), 7.32 – 7.22 (comp, 5H), 6.83 – 6.79 (comp, 2H), 3.63 – 3.53 (m, 2H), 3.38 – 3.26 (m, 3H), 2.38 (s, 3H), 2.28 – 1.92 (m, 4H). 13 C NMR (101 MHz, chloroform-d) δ 173.2, 169.5, 147.4, 138.5, 136.7, 136.6, 131.7, 129.8, 129.6, 126.4, 124.2, 118.7, 117.7, 115.2, 59.5, 51.4, 51.2, 29.1, 23.0, 21.3. HRMS (ESI, m / z) For C20H22N2O2 [M]+, the calculated value is 344.1525, and the measured value is 344.1522.

[0128] (E)-3-(2-(pyrrolidone-1-yl)benzyl)-1-(p-tolyl)pyrrolidone-2,5-dione (1zd): yellow gel (280.0 mg, 54% yield); Rf 0.30 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; single diastereomer; 1 H NMR(400 MHz, chloroform-d) δ 7.99 (t, J = 2.4 Hz,1H), 7.33 – 7.26 (comp, 6H), 6.93 (d, J = 8.2 Hz, 1H), 6.90 – 6.86 (m, 1H),3.45 (d, J = 2.4 Hz, 2H), 3.24 – 3.21 (m, 4H), 2.40 (s, 3H), 1.97 – 1.93 (m,4H). 13C NMR (101 MHz, chloroform-d) δ 173.8, 170.3, 150.0, 138.4, 136.0, 130.4, 129.8, 129.7 (X 3), 129.5, 126.3 (X 3), 122.6, 120.9, 118.5, 115.2, 52.2, 33.9, 25.6, 21.2.; HRMS (EI, m / z) Calculated value for C22H22N2O2 [M]+ 346.1681, measured value 346.1668.

[0129] Example 31 11-(3,4,5-trimethoxyphenyl)-1,2,3,12b-tetrahydrobenzo[f]dipyrrolo[1,2-a:3',4'-c]azapyridine-10,12(11H,12aH)-dione (2ze): green solid (16.0 mg, 38%); Rf 0.10 (petroleum ether / ethyl acetate = 10:3); column chromatography eluent, petroleum ether / EtOAc = 10:3; mp 128-130℃; 1 H NMR (400 MHz, chloroform-d) δ 7.70 (d, J = 2.2 Hz, 1H), 7.43 – 7.38 (m, 1H), 7.35 – 7.30 (m, 1H), 6.84 (d, J = 7.7 Hz, 1H), 6.58 (s, 1H), 3.87 (d, J = 3.2 Hz, 12H), 3.63 –3.58 (m, 2H), 3.40 (dd, J = 7.2, 2.1 Hz, 1H), 3.32 (d, J = 6.2 Hz, 1H), 2.31– 2.10 (m, 4H). 13 C NMR (101 MHz, chloroform-d) δ 173.1, 169.4, 153.4, 147.4, 136.8, 136.7, 131.8, 127.6, 123.7, 118.6, 117.7, 115.2, 104.3, 60.8, 59.3, 56.2 (X3), 51.4, 51.2, 29.0, 22.8. HRMS (ESI, m / z) For C24H24N2O5 [M]+, the calculated value is 420.1685, and the measured value is 420.1669.

[0130] (E)-3-(2-(pyrrolidone-1-yl)benzyl)-1-(3,4,5-trimethoxyphenyl)pyrrolidone-2,5-dione (1ze): Yellow solid (240.0 mg, 41% yield); Rf 0.10 (petroleum ether / ethyl acetate = 5:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 150-152℃; single diastereomer; 1 H NMR(400 MHz, chloroform-d)δ 8.00 (t, J = 2.0 Hz, 1H), 7.34 – 7.28 (comp, 2H), 6.95 – 6.86 (comp, 2H), 6.61 (s, 2H), 3.872 – 3.869 (d, J = 1.2 Hz, 9H), 3.45 (d, J = 2.4 Hz, 2H), 3.24 – 3.21 (m, 4H), 1.97 – 1.94 (m, 4H).; 13 C NMR (101 MHz, chloroform-d) δ 173.7,170.3, 153.4, 150.1, 138.0, 136.3, 130.6, 129.8, 127.6, 122.5, 120.6, 118.5,115.2, 104.2 (X 3), 60.8, 56.2 (X 2), 52.3 (X 2), 33.9, 25.6 (X 2).; HRMS (EI, m / z) for C24H26N2O5 [M]+: calculated value 422.1842, measured value 422.1832.

[0131] Example 32 11-Benzyl-1,2,3,12b-tetrahydrobenzo[f]dipyrrolo[1,2-a:3',4'-c]azapyridine-10,12(11H,12aH)-dione (2zf): yellow solid (20.0 mg, 58% yield); Rf 0.20 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 177-179℃; 1H NMR(400 MHz, chloroform-d) δ 7.58(d, J = 2.2 Hz, 1H), 7.43 – 7.41 (comp, 2H), 7.36 – 7.27 (comp, 5H), 6.81 –6.78 (m, 2H), 4.75 (AB q, J =14.0 Hz, 2H), 3.57 – 3.49 (m, 2H), 3.24 – 3.15(m, 2H), 2.24 – 2.04 (m, 3H), 2.00 – 1.89 (m, 1H). 13 C NMR (101 MHz, chloroform-d) δ 173.7, 170.0, 147.3, 136.7, 136.2, 135.9, 131.6, 128.9, 128.7 (X 2), 127.9, 124.5, 118.7, 117.7, 115.2, 59.1, 51.4, 51.3, 42.4, 29.8, 29.0, 22.9. HRMS (ESI, m / z) For C22H20N2O2 [M]+, the calculated value is 344.1525, and the measured value is 344.1601.

[0132] (E)-1-Benzyl-3-(2-(pyrrolidone-1-yl)benzylidene)pyrrolidine-2,5-dione (1zf): yellow solid (350.0 mg, 72% yield); Rf 0.30 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 114-116℃; single diastereomer; 1 H NMR(400 MHz, chloroform-d) δ 7.87 (t, J=2.3 Hz, 1H), 7.47 – 7.42 (comp, 2H), 7.35 – 7.33 (m, 1H), 7.31 – 7.27 (comp,2H), 7.24 (d, J = 7.5 Hz, 2H), 6.91 – 6.89 (m, 1H), 6.86 – 6.82 (m, 1H), 4.76 (s, 2H), 3.28 (d, J = 2.3 Hz, 2H), 3.17 (t, J = 6.5 Hz, 4H), 1.96 – 1.86 (m,4H); 13C NMR (101 MHz, chloroform-d) δ 174.2, 170.9, 150.0, 136.1, 135.3, 130.3, 129.7, 129.0, 128.6, 127.9, 122.7, 121.3, 118.5, 115.2, 52.2, 42.4, 33.8, 25.6; HRMS (EI, m / z) for C22H22N2O2 [M]+: calculated value 346.1681, measured value 346.1680.

[0133] Example 33 (E)-1-Phenylon-3-(2-(4-phenylpiperazin-1-yl)benzyl)pyrrolidine-2,5-dione (1 ozg) Yellow solid (58 mg, 45.7% yield); R f 0.30 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 162-165℃; single diastereomer; 1 H NMR (400 MHz, chloroform-) d )δ 8.16 (t, J = 2.3 Hz, 1H), 7.53 – 7.46 (m, 3H), 7.46 – 7.37 (comp, 4H), 7.31 –7.24 (comp, 2H), 7.18 – 7.14 (comp, 2H), 7.02 – 6.95 (comp, 2H), 6.90 – 6.87(m, 1H), 3.75(d, J = 2.4 Hz, 2H), 3.42 – 3.35 (m, 4H), 3.21 – 3.12 (m, 4H); 13 CNMR (101 MHz, chloroform-) d ) δ 173.2, 170.1, 153.4, 151.2, 132.6, 132.0, 131.2, 129.1, 129.1, 128.9, 128.5, 127.8, 126.6, 126.4, 123.0, 122.3, 119.3, 116.5, 53.0, 49.7, 34.0;HRMS(EI, m / z) for C 27 H 25 N3O2[M] +Calculated value: 423.1947; Measured value: 423.1945.

[0134] Example 34 3-(2-(azacycloheptane-1-yl)benzyl)-1-benzylpyrrolidine-2,5-dione (1zh) Grayish-white solid (71.8 mg, 96% yield); R f 0.30 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 140-142℃; data on major isomers, 1 H NMR (400 MHz, chloroform-) d ) δ 7.98 (s, 1H), 7.46–7.42 (comp, 3H), 7.38–7.22 (comp, 7H), 7.12 (d, J = 8.0Hz, 1H), 6.96 (t, J = 7.3 Hz, 1H), 4.78 (s, 2H), 3.49 (s, 3H), 3.26–3.07 (m,5H), 1.86 –1.64 (m, 10H); 13 C NMR (101 MHz, chloroform-) d ) δ 174.1, 170.9, 155.8,136.1, 133.7, 130.5, 128.9, 128.8, 128.6, 127.8, 127.1, 121.4, 121.1, 120.1,56.3, 42.4, 33.8, 29.1, 27.2;HRMS(EI, m / z) for C 24 H 26 N2O2[M] + The calculated value is 374.1994, and the measured value is 374.1993.

[0135] Example 35 ( E )-3-(2-(cyclohexyl(methyl)amino)benzylidene)-1-phenylpyrrolidine-2,5-dione (1zi) Grayish-white solid (63 mg, 84% yield); R f 0.30 (petroleum ether / ethyl acetate = 10:1); column chromatography eluent, petroleum ether / EtOAc = 10:1; mp 177-179℃; single diastereomer;1 H NMR (400 MHz, chloroform-) d )δ 8.07 (t, J = 2.2 Hz, 1H), 7.53 – 7.48 (comp, 2H), 7.47 – 7.44 (m, 1H), 7.44 –7.33 (comp, 4H), 7.14 (app d, J = 8.1 Hz, 1H), 7.08 – 7.04 (m, 1H), 3.74 (d, J =2.3 Hz, 2H), 2.79 (dt, J = 11.6, 3.4 Hz, 1H), 2.75 (s, 3H), 1.80 (dd, J =25.0, 11.5 Hz, 4H), 1.64 – 1.43 (m, 3H), 1.11 (p, J = 12.6 Hz, 3H); 13 C NMR (101MHz, chloroform-) d ) δ 173.5, 170.2, 154.5, 133.8, 132.2, 130.4, 129.0, 128.9, 128.3, 128.2, 126.4, 121.6, 121.2, 121.0, 65.3, 34.1, 34.0, 29.4, 26.0, 25.9;HRMS(ESI, m / z) for C 24 H 26 N2O2[M] + The calculated value is 374.1994, and the measured value is 374.1993.

[0136] Example 36 3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(4-nitrophenyl)pyrrolidine-2,5-dione (1zj) Yellow solid (65.9 mg, 75% yield); R f 0.30 (petroleum ether / ethyl acetate = 5:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; mp 192-195℃; data on major isomers. 1 H NMR (400 MHz, chloroform-) d ) δ8.36 – 8.32 (comp, 2H), 8.16 (t, J= 2.4 Hz, 1H), 7.75 – 7.70 (comp, 2H), 7.50 – 7.47 (m, 1H), 7.45 – 7.39 (m, 1H), 7.23 – 7.13 (comp, 5H), 7.12 – 7.08 (m,1H), 4.28 (s, 2H), 3.79 (d, J = 2.4 Hz, 2H), 3.27 (t, J = 5.8 Hz, 2H), 3.04 (t, J =5.7 Hz, 2H); 13 C NMR (101 MHz, chloroform-) d ) δ 172.5, 169.3, 153.5, 146.7, 137.7, 134.3, 134.2, 134.2, 131.5, 129.1, 129.1, 127.2, 126.7, 126.5, 126.3, 126.0, 124.2, 122.5, 121.0, 119.4, 53.5, 53.1, 34.1, 29.3;HRMS(EI, m / z) for C 26 H 21 N3O4[M] + Calculated value: 439.1532; measured value: 439.1536.

[0137] Example 37 (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)pyrrolidine-2,5-dione (1zk) Grayish-white solid (44.5 mg, 70% yield); R f 0.30 (petroleum ether / ethyl acetate = 5:1); column chromatography eluent, petroleum ether / EtOAc = 5:1; mp 152-155℃; single diastereomer; 1 H NMR (400 MHz, chloroform-) d ) δ8.88 (s, 1H), 7.97 (app t, J = 2.2 Hz, 1H), 7.66 – 7.60 (comp, 2H), 7.56 – 7.50(comp, 2H), 7.41 (app t, J= 8.0 Hz, 1H), 7.20 – 7.16 (comp, 2H), 7.13 – 7.07(m, 1H), 4.26 (s, 2H), 3.59 (d, J = 2.4 Hz, 2H), 3.24 (t, J = 5.8 Hz, 2H), 3.06 –2.98 (m, 2H); 13 C NMR (101 MHz, chloroform-) d ) δ 174.5, 171.2, 153.2, 134.3, 133.4, 133.3, 132.8, 132.7, 131.0, 129.3, 129.0, 126.4, 125.9, 123.5, 122.4, 119.3, 53.5, 52.8, 34.9, 29.1;HRMS(EI, m / z) for C 20 H 18 N2O2[M] + The calculated value is 318.1368, and the measured value is 318.1366.

[0138] Example 38 (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(4-(dimethylamino)phenyl)pyrrolidine-2,5-dione (1zl) Yellow solid (140.0 mg, 64% yield); R f 0.10 (petroleum ether / ethyl acetate = 9:1); column chromatography eluent, petroleum ether / EtOAc = 9:1; single diastereomer; 1 H NMR (400 MHz, chloroform-) d ) δ 8.08 (t, J =2.3 Hz, 1H), 7.49 (dd, J = 7.7, 1.3 Hz, 1H), 7.42 – 7.38 (m, 1H), 7.24 – 7.14(comp, 7H), 7.13 – 7.09 (comp, 2H), 6.82 – 6.75 (comp, 2H), 4.29 (s, 2H), 3.72 (d, J = 2.4 Hz, 2H), 3.27 (t, J = 5.8 Hz, 2H), 3.05 (t, J= 5.7 Hz, 2H), 2.99 (s, 6H). 13 C NMR (101 MHz, chloroform-) d ) δ 173.9, 170.7, 153.2, 150.4, 134.5, 134.4,132.4, 130.8, 129.1, 127.7, 127.0, 126.4, 126.3, 125.9, 122.5, 122.4, 120.6,119.2, 112.4, 53.4, 53.0, 40.5, 34.0, 29.2. Example 39 (E)-2-(4-(3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-2,5-dioxopyrrolidine-1-yl)phenyl)-6-(dimethylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione (1zm) Off-white solid (50.0 mg, 80% yield); R f 0.30 (petroleum ether / ethyl acetate = 1:1); column chromatography eluent, petroleum ether / EtOAc = 1:1; single diastereomer; 1 H NMR (400 MHz, chloroform-) d ) δ 8.64 – 8.61(m, 1H), 8.54 – 8.48 (comp, 2H), 8.14 (s, 1H), 7.73 – 7.64 (comp, 3H), 7.51(d, J = 6.9 Hz, 1H), 7.47 – 7.39 (comp, 3H), 7.22 – 7.10 (comp, 7H), 4.30 (s,2H), 3.78 (d, J = 2.2 Hz, 2H), 3.29 (t, J = 5.8 Hz, 2H), 3.14 (s, 6H), 3.06 (t, J =5.6 Hz, 2H). 13 C NMR (101 MHz, chloroform-) d) δ 173.0, 169.8, 164.6, 164.0, 157.3,153.3, 135.3, 134.4, 134.3, 133.2, 133.1, 132.1, 131.4, 131.5, 131.0, 129.5,129.1, 127.6, 126.7, 126.4, 126.3, 125.9, 125.4, 124.9, 123.1, 122.4, 122.0,119.2, 114.8, 113.3, 53.4, 53.0, 44.8, 34.0, 29.7, 29.2. Advantages of the present invention This invention addresses the challenges of synthesizing dihydrobenzo[b,e]pyrrolo-nitrogen hybrids with maleimide / succinimide and tetrahydroisoquinoline as well as other cyclic / acyclic amine moieties. It employs an environmentally friendly, harmless, zero-carbon-footprint electrochemical method that enables efficient production from readily available starting materials in a short time.

[0139] The innovation lies in the fact that no conventional reagents, such as acids, transition metal catalysts, oxidants, or bases, are used in this highly efficient conversion.

[0140] The synthesis method of this invention is relatively simple to operate, has mild reaction conditions, high yield, and is direct, making it suitable for large-scale production. It uses readily available electrolytes under mild conditions, making it more economical than other reagents.

[0141] The novel dihydrobenzo[b,e]pyrroloza hybrid is an excellent probe for detecting picric acid and other nitro compounds.

[0142] The method exhibits good tolerance to a wide range of functional groups in terms of substrate scope. Therefore, this methodology is of great significance for generating various derivative compounds of dihydrobenzo[b,e]pyrroloza.

[0143] • It uses readily available electrolytes under mild conditions, which are cheaper than other reagents. The reaction does not use oxidizing agents, reducing agents, transition metals, Lewis acids, or expensive reagents. The reaction proceeds smoothly under atmospheric pressure and mild conditions.

[0144] This is a direct, economical, and simple one-pot method; therefore, it is effective for industrial production.

Claims

1. A compound of formula 2 in R 1 and R 2 Independently selected from the group consisting of: hydrogen, straight-chain or branched (C1-C12) alkyl, perfluoro(C1-C12) alkyl, (C3-C12) cycloalkyl, (C6-C12) bicycloalkyl, (C3-C14) tricycloalkyl, (C6-C10) aryl; perfluoro(C6-C10) aryl, perfluoro(C6-C10) aryl(C1-C3) alkyl, (C5-C10) heteroaryl, (C5 -C10) heteroaryl (C1-C3) alkyl, hydroxyl, (C1-C12) alkoxy, (C3-C12) cycloalkoxy, (C6-C12) bicycloalkoxy, (C7-C14) tricycloalkoxy, (C6-C10) aryloxy (C1-C3) alkyl, (C6-C10) aryloxy, (C5-C10) heteroaryloxy, (C1-C6) acyloxy, halogen, nitro or amino; R 3 Independently selected from the group consisting of: hydrogen, halogen-containing aryl, nitro, amino, all kinds of organic functional groups, straight-chain or branched (C1-C12) alkyl, perfluoro(C1-C12) alkyl, (C3-C12) cycloalkyl, (C6-C12) bicycloalkyl, (C3-C14) tricycloalkyl, (C6-C10) aryl; perfluoro(C6-C10) aryl, perfluoro(C6-C10) aryl(C1-C3) alkyl. alkyl, (C5-C10)heteroaryl, (C5-C10)heteroaryl, (C1-C3)alkyl, hydroxyl, (C1-C12)alkoxy, (C3-C12)cycloalkoxy, (C6-C12)bicycloalkoxy, (C7-C14)tricycloalkoxy, (C6-C10)aryloxy, (C1-C3)alkyl, (C6-C10)aryloxy, (C5-C10)heteroaryloxy, (C1-C6)acyloxy; n = 0, 1, 2, 3, 4 or 5; X = C or N.

2. The compound of claim 1, wherein the representative compound of formula 2 is selected from the group consisting of: i.6-Phenyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2a); ii.6-(4-methoxyphenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2b); iii. 6-(4-bromophenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2c); iv. 6-(4-fluorophenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-zircono[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2d); v.6-(4-(trifluoromethyl)phenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2e); vi. 6-(3,4,5-trimethoxyphenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2f); vii. 6-Benzyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2g); viii. 6-Methyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2h); ix.6-Ethyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2i); x.6-propyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2j); xi.6-hexyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2k); xii. 6-Heptyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2l); xiii. 6-Octy-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2m); xiv. 6-(2-methoxyethyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2n); XV. 3-(5,7-dioxo-4c,5,14,15-tetrahydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-aziro[2,1-a]isoquinoline-6(7H)-yl)propionate ethyl ester (2o); xvi.10-Chloro-6-ethyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2p); xvii.10-Chloro-6-phenyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2q); xviii.6-Benzyl-11-chloro-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2r); xix.3-Methyl-6-phenyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2s); xx.2,3-Dimethoxy-6-phenyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2t); xxi.2,3-Dimethoxy-6-methyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2u); xxii.2,3-Dimethoxy-6-(3,4,5-trimethoxyphenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2v); xxiii.6-(4-phenylbutyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione (2w); xxiv.6-Phenylacetyl-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2x); xxv.6-(2-(thiophen-2-yl)ethyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-zirco[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2y); xxvi.6-(3-methoxyphenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2z); xxvii.6-Phenyl-14,15-dihydro-4bH-pyrido[3',2':6,7]pyrrolo[3',4':3,4]aza-zircono[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2za); xxviii.6-(4-chlorophenyl)-14,15-dihydro-4bH-benzo[6,7]pyrrolo[3',4':3,4]aza-benzo[2,1-a]isoquinoline-5,7(4cH,6H)-dione(2zb); xxix.11-Phenyl-1,2,3,12b-tetrahydrobenzo[f]dipyrrolo[1,2-a:3',4'-c]azapyridine-10,12(11H,12aH)-dione(2zc); xxx.11-(p-Tolyl)-1,2,3,12b-tetrahydrobenzo[f]dipyrrolo[1,2-a:3',4'-c]aza-10,12(11H,12aH)-dione(2zd); xxxi.11-(3,4,5-trimethoxyphenyl)-1,2,3,12b-tetrahydrobenzo[f]dipyrrolo[1,2-a:3',4'-c]azapyridine-10,12(11H,12aH)-dione(2ze); xxxii.11-Benzyl-1,2,3,12b-tetrahydrobenzo[f]dipyrrolo[1,2-a:3',4'-c]aza-10,12(11H,12aH)-dione(2zf).

3. An electrochemical method for synthesizing the compound of formula 2 as described in claim 1, the method comprising the following steps: i. Mix Formulas 3, 4, and 5 with the solvent in a round-bottom flask equipped with an electromagnetic stirrer to obtain a mixture; Where R 1 R 2 and R 3 Same as defined above. ii. Stir the mixture obtained in step (i) for a period of time ranging from 12 to 24 hours to obtain a solid precipitate; iii. Filter the solid precipitate obtained in step (ii) and then wash it with cold ethanol to obtain the compound of formula 1; iv. Add Formula 1, electrolyte, optionally along with electrocatalyst and organic solvent to a 5 mL oven-dried electrochemical reaction vial, using a graphite rod as both anode and cathode, to obtain a mixture; v. The mixture obtained in step (iv) is then electrolyzed at ambient temperature with a constant current of 1 mA or 1-10 mA for a period of time ranging from 10 h to 24 h to obtain the compound of formula 2.

4. The method of claim 3, wherein the electrolyte used is selected from the group consisting of: ammonium salts of formula 6, tetrabutylammonium tetrafluoroborate (TBABF4), tetrabutylammonium hexafluorophosphate (TBAPF6), tetrabutylammonium perchlorate (TBAClO4), tetrabutylammonium iodide (TBAI), tetrabutylammonium bromide (TBAB), tetrabutylammonium acetate (TBAOAc), ammonium acetate (NH4OAc), ammonium iodide (NH4I), or quaternary ammonium alkaloids or metal salts. Formula 6 Where R = hydrogen, straight-chain or branched (C1-C12) alkyl, perfluoro(C1-C12) alkyl, (C3-C12) cycloalkyl, (C6-C12) bicycloalkyl, (C3-C14) tricycloalkyl, (C6-C10) aryl; perfluoro(C6-C10) aryl, perfluoro(C6-C10) aryl(C1-C3) alkyl, (C5-C10) heteroaryl, (C5-C10) Heteroaryl (C1-C3)alkyl, hydroxyl, (C1-C12)alkoxy, (C3-C12)cycloalkoxy, (C6-C12)bicycloalkoxy, (C7-C14)tricycloalkoxy, (C6-C10)aryloxy, (C1-C3)alkyl, (C6-C10)aryloxy, (C5-C10)heteroaryloxy, (C1-C6)acyloxy, halogen, nitro or amino.

5. The method of claim 4, wherein the metal salt used is selected from the group consisting of: lithium perchlorate (LiClO4), sodium perchlorate (NaClO4), lithium chloride (LiCl), sodium chloride (NaCl), potassium chloride (KCl), potassium iodide (KI), sodium iodide (NaI), potassium fluoride (KF), potassium phosphate, sodium acetate (NaOAc), and magnesium chloride (MgCl2).

6. The method of claim 3, wherein the organic solvent used is selected from the group consisting of: TFE, MeOH, 1,4-dioxane, toluene, benzene, acetonitrile, THF, 2-MeTHF, dimethylformamide (DMF), dimethyl sulfoxide, ethyl acetate or acetone, alone or in combination thereof, preferably TFE / MeOH.

7. The method of claim 3, wherein the electrocatalyst used is selected from the group consisting of ABNO, ferrocene, PIDA, or TEMPO.

8. The method of claim 3, wherein the compound of formula 1 is selected from the group consisting of: i.( E )-3-(2-(3,4-dihydroisoquinoline-2(1 H )-yl)benzylidene)-1-phenylpyrrolidine-2,5-dione (1a); ii. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(4-methoxyphenyl)pyrrolidine-2,5-dione (1b); iii. (E)-1-(4-bromophenyl)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)pyrrolidine-2,5-dione (1c); iv. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(4-fluorophenyl)pyrrolidine-2,5-dione (1d); v.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-(4-(trifluoromethyl)phenyl)pyrrolidine-2,5-dione(1e); vi. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-(3,4,5-trimethoxyphenyl)pyrrolidine-2,5-dione (1f); vii.( E )-1-benzyl-3-(2-(3,4-dihydroisoquinoline-2(1 H )-yl)benzylidene)pyrrolidine-2,5-dione (1g); viii. (E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-methylpyrrolidine-2,5-dione (1h); ix.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-ethylpyrrolidine-2,5-dione (1i); x.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-propylpyrrolidine-2,5-dione (1j); xi.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-hexylpyrrolidine-2,5-dione(1k); xii.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-heptylpyrrolidine-2,5-dione (1l); xiii.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-octylpyrrolidine-2,5-dione(1m); xiv.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-(2-methoxyethyl)pyrrolidine-2,5-dione(1n); xv.(E)-3-(3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-2,5-dioxopyrrolidone-1-yl)ethyl propionate (1o); xvi.(E)-3-(5-chloro-2-(3,4-dihydroisoquinolin-2(1H)-yl)benzyl)-1-ethylpyrrolidine-2,5-dione(1p); xvii.(E)-3-(5-chloro-2-(3,4-dihydroisoquinolin-2(1H)-yl)benzyl)-1-phenylpyrrolidine-2,5-dione(1q); xviii.( E )-1-benzyl-3-(4-chloro-2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)pyrrolidine-2,5-dione(1r); xix.(E)-3-(2-(7-methyl-3,4-dihydroisoquinoline-2(1H)-yl)benzyl)-1-phenylpyrrolidine-2,5-dione(1s); xx.( E )-3-(2-(6,7-dimethoxy-3,4-dihydroisoquinoline-2(1 H )-yl)benzylidene)-1-phenylpyrrolidine-2,5-dione (1t); xxi.(E)-3-(2-(6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-methylpyrrolidine-2,5-dione (1u); xxii.A(E)-3-(2-(6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(3,4,5-trimethoxyphenyl)pyrrolidine-2,5-dione(1v); xxiii.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(4-phenylbutyl)pyrrolidine-2,5-dione (1w); xxiv.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-phenylethylpyrrolidine-2,5-dione (1x); xxv.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(2-(thiophen-2-yl)ethyl)pyrrolidine-2,5-dione(1y); xxvi.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(3-methoxyphenyl)pyrrolidine-2,5-dione (1z); xxvii.(E)-3-((2-(3,4-dihydroisoquinoline-2(1H)-yl)pyridin-3-yl)methylene)-1-phenylpyrrolidine-2,5-dione(1za); xxviii.(E)-1-(4-chlorophenyl)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)pyrrolidine-2,5-dione (1zb); xxix.(E)-1-phenyl-3-(2-(pyrrolidone-1-yl)benzylidene)pyrrolidone-2,5-dione (1zc); xxx.(E)-3-(2-(pyrrolidone-1-yl)benzylidene)-1-(p-tolyl)pyrrolidone-2,5-dione (1zd); xxxi.(E)-3-(2-(pyrrolidine-1-yl)benzylidene)-1-(3,4,5-trimethoxyphenyl)pyrrolidine-2,5-dione (1ze); xxxii.(E)-1-benzyl-3-(2-(pyrrolidine-1-yl)benzylidene)pyrrolidine-2,5-dione (1zf); xxxiii.(E)-1-phenyl-3-(2-(4-phenylpiperazin-1-yl)benzylidene)pyrrolidine-2,5-dione (1 ozg); xxxiv.3-(2-(azacycloheptane-1-yl)benzylidene)-1-benzylpyrrolidine-2,5-dione (1zh); xxxv.(E)-3-(2-(cyclohexyl(methyl)amino)benzylidene)-1-phenylpyrrolidine-2,5-dione (1zi); xxxvi.3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(4-nitrophenyl)pyrrolidine-2,5-dione (1zj); xxxvii.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)pyrrolidine-2,5-dione (1zk); xxxviii.(E)-3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-1-(4-(dimethylamino)phenyl)pyrrolidine-2,5-dione (1zl); xxxix.(E)-2-(4-(3-(2-(3,4-dihydroisoquinoline-2(1H)-yl)benzylidene)-2,5-dioxopyrrolidine-1-yl)phenyl)-6-(dimethylamino)-1H-benzo[de]isoquinoline-1,3(2H)-dione (1zm).

9. The method of claim 3, wherein the yield of the compound of formula 1 is in the range of 40%-90%.

10. The method of claim 3, wherein the yield of the compound of formula 2 is in the range of 40%-87%.

11. The compound of claim 1, wherein the compounds of formula 2 and formula 1 are used as potential bioactive molecules and potential molecular probes as well as chemical sensors for the detection of picric acid and other nitro compounds.

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