An improved synthesis of 2‐amino‐5‐[(4‐chlorophenyl)thio]‐4‐morpholinopyrimidine (BW 394U) — A potential antisenility agent

This paper describes the synthesis of 2‐amino‐5‐[(4‐chlorophenyl)thio]‐4‐morpholinopyrimidine (BW 394U, compound 4 ), a potential antisenility agent. The key intermediates 3a/3b were obtained from an in situ‐generated Vilsmeier‐Haack reagent that simultaneously protected the 2‐amino group prior to further manipulations. Displacement of the chloro group in 3a gave 4 in 40% yield and 4‐dimethylamino analogue 5. However, displacement of 3b with morpholine followed by treatment with aqueous base gave 4 in 74% yield.     

Synthesis and pharmacological investigation of novel 4‐(4‐Ethyl phenyl)‐1‐substituted‐4H‐[1,2,4]triazolo[4,3‐a]‐quinazolin‐5‐ones as new class of H1‐antihistaminic agents

A series of novel 4‐(4‐ethylphenyl)‐1‐substituted‐4H‐[1,2,4]triazolo[4,3‐a]quinazolin‐5‐ones were synthesized by the cyclization of 2‐hydrazino intermediate with various electrophile. The starting material 2‐hydrazino compound was synthesized from 2‐ethyl aniline by a new innovative route with improved yield. When tested for their in vivo H₁‐antihistaminic activity on conscious guinea pigs, all the test compounds significantly protected the animals from histamine induced bronchospasm. The compound II emerged as the most active compound of the series and it is more potent (73.93% protection) when compared to the reference standard, chlorpheniramine maleate (71% protection), it showed negligible sedation (10%) when compared to chlorpheniramine maleate (30%). Therefore compound II will serve as prototype molecule for further development as a new class of H₁‐antihistamines     

A scalable Nenitzescu synthesis of 2‐methyl‐4‐(trifluoromethyl)‐1H‐indole‐5‐carbonitrile

2‐Methyl‐4‐(trifluoromethyl)‐1H‐indole‐5‐carbonitrile is a key intermediate in the synthesis of selective androgen receptor modulators discovered in these laboratories. A practical and convergent synthesis of the title compound starting from 4‐nitro‐3‐(trifluoromethyl)phenol and tert‐butyl acetoacetate was developed, including a telescoped procedure for synthesis (without isolation) and Nenitzescu reaction of 2‐trifluoromethyl‐1,4‐benzoquinone. Conversion of the known Nenitzescu indole product to a novel triflate intermediate followed by palladium‐catalyzed cyanation afforded a penultimate carbonitrile. Removal of the C‐3 tert‐butyl ester group on the indole through a decarboxylative pathway completed the synthesis of the title compound in six steps (27% overall yield) from 4‐nitro‐3‐(trifluoromethyl)phenol (five steps, 37% overall yield from tert‐butyl acetoacetate). J. Heterocyclic Chem., (2011).     

Green approach for the synthesis of 3‐methyl‐1‐phenyl‐4‐((2‐phenyl‐1H‐indol 3‐yl)methylene)‐1H‐pyrazole‐5(4H)‐ones and their DNA Cleavage,antioxidant, and antimicrobial activities

3‐Methyl‐1‐phenyl‐4‐((2‐phenyl‐1H‐indol‐3‐yl)methylene)‐1H‐pyrazol‐5(4H)‐ones (5a‐i) was prepared by the condensation reaction of different 3‐formyl‐2‐phenylindole derivatives (2a‐i) and 3‐methyl‐1‐phenyl‐2‐pyrazoline‐5‐one in quantitative yield by applying various green synthetic methods as grinding, microwave irradiation using different catalysts under solvent‐free mild reaction conditions with high product yields. The structures of the synthesized compounds were characterized on the basis of elemental analysis, infrared, ¹HNMR, ¹³C NMR, and mass spectral data. The synthesized compounds were screened for free radical scavenging, antimicrobial, and DNA cleavage activities. Most of the tested compounds belonging to the 3‐methyl‐1‐phenyl‐4‐((2‐phenyl‐1H‐indol‐3‐yl)methylene)‐1H‐pyrazol‐5(4H)‐ones series exhibited promising activities.     

1,3‐Dihydro‐2H‐imidazo[4,5‐c]pyridin‐2‐one

A facile acid catalysed cyclisation method for the preparation of the cyclic urea 2H‐imidazo[4,5‐c]pyridin‐2‐one ( 2 ) in > 95 % yield is reported. The biologically active compound 2 can be obtained by heating (3‐amino‐4‐pyridinyl)‐carbamic acid methyl, ethyl or tert‐butyl esters ( 1a‐c ) in sulfuric acid (0.1 %) or in aqueous HBF₄ (3.5 equivalents) for 10 min. ‐ 3 hrs at 90 °C. The corresponding microwave‐promoted (MW) reactions afforded the pure product 2 within few minutes. The 6‐butylamino‐substituted analogue ( 2a ) was correspondingly obtained by MW irradiation in 99 % yield by cyclisation of 2‐(butylamino)‐5‐amino‐4‐pyridylcarbamic acid isopropyl ester ( 1d ). Quantitative precipitation of product 2 was obtained by pH adjustment. The process represents a solvent‐free, “green” method for the preparation of 2 .     

Enantioselective Synthesis of (−)‐(19R)‐Ibogamin‐19‐ol

The first total synthesis of the natural product (?)‐(19R)‐ibogamin‐19‐ol ((?)‐ 1 ) is reported (biogenetic atom numbering). Starting with L ‐glutamic acid from the chiral pool and (2S)‐but‐3‐en‐2‐ol, the crucial aliphatic isoquinuclidine (= 2‐azabicyclo[2.2.2]octane) core containing the entire configurational information of the final target was prepared in 15 steps (overall yield: 15%). The two key steps involved a highly effective, self‐immolating chirality transfer in an Ireland–Claisen rearrangement and an intramolecular nitrone‐olefin 1,3‐dipolar cycloaddition reaction (Scheme 3). Onto this aliphatic core was grafted the aromatic moiety in the form of N(1)‐protected 1H‐indole‐3‐acetic acid by application of the dicyclohexylcarbodiimide (DCC) method (Scheme 4). Four additional steps were required to adjust the substitution pattern at C(16) and to deprotect the indole subunit for the closure of the crucial 7‐membered ring present in the targeted alkaloid family (Schemes 4 and 5). The spectral and chiroptical properties of the final product (?)‐ 1 matched the ones reported for the naturally occurring alkaloid, which had been isolated from Tabernaemonatana quadrangularis in 1980. The overall yield of the entire synthesis involving a linear string of 20 steps amounted to 1.9% (average yield per step: 82%).     

Preparation of 2‐phenyl‐2‐hydroxymethyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline and 2‐methyl‐4‐oxo‐3,4‐dihydroquinazoline derivatives formation

The cyclization of phenacyl anthranilate has been studied with the aim to develop the synthesis of 2‐(2′‐aminophenyl)‐4‐phenyloxazole. However, a different course of the reaction than expected was observed. 2‐Phenyl‐2‐hydroxymethyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline ( 3a ) was formed by the reaction of phenacyl anthranilate ( 2 ) with ammonium acetate under various conditions. 3‐Hydroxy‐2‐phenyl‐4(1H)‐quinolinone ( 4 ) arose by heating compound 3a in acetic acid. The same compound was obtained by melting compound 3a , but the yield was lower. Different types of products resulted in the reaction of compound 3a with acetic anhydride. Under mild conditions acetylated products 2‐acetoxymethyl‐2‐phenyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline ( 7a ) and 2‐acetoxymethyl‐3‐acetyl‐2‐phenyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline ( 8 ) were prepared. If the reaction was carried out under reflux of the reaction mixture, molecular rearrangement took place to give cis and trans 2‐methyl‐4‐oxo‐3‐(1‐phenyl‐2‐acetoxy)vinyl‐3,4‐dihydroquinazolines ( 9a and 9b ). All prepared compounds have been characterised by their ¹H, ¹³C and ¹⁵N NMR spectra, IR spectra and MS.     

Design and Synthesis of Novel 3‐(Phenyl)‐2‐(3‐substituted propylthio) Quinazolin‐4‐(3H)‐ones as a New Class of H1‐Antihistaminic Agents

A series of novel 3‐(phenyl)‐2‐(3‐substituted propylthio) quinazolin‐4‐(3H)‐ones were synthesized by the reaction of 2‐(3‐bromopropylthio)‐3‐(phenyl) quinazolin‐4‐(3H)‐one with various amines. The starting material, 2‐(3‐bromopropylthio)‐3‐(phenyl) quinazolin‐4‐(3H)‐one was synthesized from aniline. When tested for their in vivo H₁‐antihistaminic activity on conscious guinea pigs, all the test compounds protected the animals from histamine‐induced bronchospasm significantly. Compound 2‐(3‐(4‐methylpiperazin‐1‐yl) propylthiothio)‐3‐(phenyl) quinazolin‐4(3H)‐one ( Ph5 ) emerged as the most active compound (73.23% protection) of the series when compared with the reference standard chlorpheniramine maleate (70.09% protection). Compound Ph5 shows negligible sedation (5.01 %) compared with chlorpheniramine maleate (29.58%). Therefore, compound Ph5 can serve as the leading molecule for further development into a new class of H₁‐antihistaminic agents.     

Reliable Chemical Synthesis of Oligoribonucleotides (RNA) with 2′‐O‐[(Triisopropylsilyl)oxy]methyl(2′‐O‐tom)‐Protected Phosphoramidites

A method for the introduction of the 2′‐O‐[(triisopropylsilyl)oxy]methyl (=tom) group into N‐acetylated, 5′‐O‐dimethoxytritylated ribonucleosides is presented. The corresponding 2′‐O‐tom‐protected phosphoramidite building blocks were obtained in pure form and were successfully employed for the routine synthesis of oligoribonucleotides on DNA synthesizers. Under DNA coupling conditions (2.5 min coupling time for a 1.5‐μmol synthesis scale) and with 5‐(benzylthio)‐1H‐tetrazole (BTT) as activator, 2′‐O‐tom‐protected phosphoramidites exhibited average coupling yields >99.4%. The combination of N‐acetyl and 2′‐O‐tom protecting groups allowed a reliable and complete two‐step deprotection, first with MeNH₂ in EtOH/H₂O and then with Bu₄NF in THF, without concomitant destruction of the product RNA sequences.     

Synthesis of 15‐Cyano‐12‐oxopentadecano‐15‐lactone and 15‐Cyano‐ 12‐oxopentadecano‐15‐lactam

15‐Cyano‐12‐oxopentadecano‐15‐lactone was synthesized in 59% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by reaction with trimethylsilylcyanide, hydrolysis, ring‐expansion, and Nef reaction. A two‐step, one‐pot synthesis of intermediate 2‐hydroxy‐4‐(1‐nitro‐2‐oxycyclododecyl)butanenitrile from 3‐(1‐nitro‐2‐oxocyclododecyl)propanal was developed and the conditions for the Nef reaction were studied. 15‐Cyano‐12‐oxopentadecano‐15‐lactam was synthesized in 40% total yield starting from 2‐nitrocyclododecanone by Michael addition to acrylaldehyde, followed by Strecker reaction, ring‐expansion, and Nef reaction. The conditions for the Strecker and Nef reactions were studied. The structures of the target compounds, intermediates, and by‐product were characterized by IR, ¹H‐ and ¹³C‐NMR, and elemental analysis or MS.     

Synthesis and Fungicidal Activity of (1Z, 3Z)‐4,4‐Dimethyl‐1‐substitutedphenyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐pent‐1‐en‐3‐one O‐[2,4‐dimethylthiazole(or 4‐methyl‐1,2,3‐thiadiazole)]‐5‐carbonyl Oximes

A series of novel (Z)‐1‐tert‐butyl (or phenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐ethanone O‐[2,4‐dimethylthiazole (or 4‐methyl‐1,2,3‐thiadiazole) ?5‐carbonyl] oximes 5a – 5c and (1Z, 3Z)‐4,4‐dimethyl‐1‐substitutedphenyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐pent‐1‐en‐3‐one O‐[2,4‐dimethylthiazole (or 4‐methyl‐1,2,3‐thiadiazole)‐5‐carbonyl] oximes 6a – 6e were synthesized by the condensations of (Z)‐1‐tert‐butyl (or phenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐ethanone oximes 3 or (1Z, 3Z)‐4,4‐dimethyl‐1‐substitutedphenyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐pent‐1‐en‐3‐one oximes 4 with 2,4‐dimethylthiazole‐5‐carbonyl chloride or 4‐methyl‐1,2,3‐thiadiazole‐5‐carbonyl chloride in the basic condition. Their structures were confirmed by IR, ¹H NMR, mass spectroscopy, and elemental analyses. The results of preliminary bioassays showed the title compounds 5 and 6 exhibited moderate to good fungicidal activities. For example, compound 6c possessed 86.4% inhibition against Fusarium oxysporum, and compound 6b exhibited 86.4 and 100% inhibition against Fusarium oxysporum and Cercospora arachidicola Hori at the concentration of 50 mg/L, respectively.     

The Thermal N9/N7 Isomerization of N2‐Acylated 2′‐Deoxyguanosine Derivatives in the Melt and in Solution

The protected 2′‐deoxyguanosine derivatives 5a – c undergo N⁹→N⁷ isomerization in the melt and in solution. The rate of isomerization is much faster than in the case of the corresponding ribonucleosides and occurs even in the absence of a catalyst. In the melt (195°, 2 min), the N²,3′‐O,5′‐O‐tris(4‐toluoyl) derivative 5b and the N²‐acetyl‐3′,5′‐bis‐O‐[(tert‐butyl)dimethylsilyl] derivative 5c gave anomeric mixtures of the N⁷‐isomers 9b / 10b (43%) and 9c / 10c (55%), respectively. In addition, the N⁹‐α‐D ‐anomers 8b and 8c were obtained. Different from 5b , the isomerization of peracetylated 5a resulted in low yields. Compound 5b was also prone to isomerization performed in solution (toluene, 100°, 5 min; chlorobenzene, 120°, 5 min), furnishing the N⁷‐regioisomers in 24–53% yield. The highest yield of the N⁹→N⁷ isomerization occurred in the presence of 2‐deoxy‐3,5‐di‐O‐(4‐toluoyl)‐α‐D ‐erythro‐pentofuranosyl chloride.     

Facile Synthesis of Novel 3‐(4‐phenylisothiazol‐5‐yl)‐2H‐chromen‐2‐one Derivatives as Potential Anticancer Agents

A series of 3‐(4‐phenylisothiazol‐5‐yl)‐2H‐chromen‐2‐one ( 6a – l ) derivatives has been efficiently synthesized by straightforward sequential reactions. Tandem Vilsmeier Hack reaction/cyclization/bromination/Suzuki cross‐coupling reactions were successfully applied to the preparation of title compounds in good‐to‐high yields. In the synthetic sequences, 3‐chloro‐3‐(2‐oxo‐2H‐chromen‐3‐yl)acrylaldehydes ( 2 ) were found to react with ammonium thiocyanate to yield the corresponding 3‐(isothiazol‐5‐yl)‐2H‐chromen‐2‐ones ( 3 ). These derivatives were brominated with N‐bromo succinamide to yield the corresponding regioselective 3‐(4‐bromoisothiazol‐5‐yl)‐2H‐chromen‐2‐one ( 4 ). Finally, compound 4 was treated with various phenyl/pyrazole/7H –pyrrolo[2,3‐d]pyrimidinyl boronic acids 5a – l in the presence of K₂CO₃ and Pd catalyst in dimethylformamide to yield the corresponding title derivatives 6a – l . All the synthesized compounds were characterized by analytical and spectral studies. All the final compounds were screened against different cancer cell lines (A549, PC3, SKOV3, and B16F10), and among these compounds, 6b , 6g , 6h , and 6l displayed moderate cytotoxic activity against the tested cell lines.     

Studies with Polyfunctionally Substituted Heteroaromatics: The Reaction of Heterocyclic Enaminonitriles with α‐β‐Unsaturated Nitriles

5‐Amino‐4‐cyano‐3‐phenylpyrazole ( 1 ) reacts with cinnamonitriles ( 2 ) to yield the pyrazolo[1,5‐a]pyrimidines ( 3 ). Also, 5‐amino‐4‐cyano‐1‐phenylpyrazole ( 4 ) reacts with cinnamonitriles ( 2 ) to yield the pyrazolo[3,4‐b]pyridine derivatives ( 5 ). In contrast to this reaction, enaminothiophene ( 6 ) reacts with cinnamonitriles ( 2 ) to yield compound ( 7 ) not ( 8 ). The enaminopyrane ( 9 ) reacts with cinnamonitriles ( 2 ) to yield ( 10 ). Finally we have attempted to add cinnamonitriles ( 2 ) to thiopyrane ( 13 ); only rearrangement and aromatization product ( 14 ) was isolated.     

Synthesis and Fungicidal Activity of (E)‐5‐[1‐(2‐Oxo‐1‐oxaspiro[4,5]dec/non‐3‐en‐3‐yl)ethylidene]‐2‐aminoimidazolin‐4‐one Derivatives

The novel fungicidal agents, (E )‐5‐[1‐(2‐oxo‐1‐oxaspiro[4,5]dec/non‐3‐en‐3‐yl)ethylidene]‐2‐aminoimidazolin‐ 4‐one derivatives, were designed and synthesized in moderate to excellent yields in four steps using α ‐hydroxyketone and diketene as raw materials and characterized by HR‐ESI‐MS , ¹H NMR and X‐ray diffraction. The preliminary bioassay showed that some of these compounds, such as 5e , 6a , 6e , and 7 h exhibit 87.8%, 91.3%, 89.9% and 87.8% inhibition rates against Sclerotinia scleotiorum , 3b , 3c , 4c and 7 h exhibit 96.4%, 92.5%, 90.3% and 76.9% inhibition rates against Phytophthora capsici at the concentration of 50 µg/mL , respectively. These compounds exhibited significant fungicidal activities against S. scleotiorum and P. capsici with EC₅₀ values of 2.56–11.60 µg/mL , and compounds 6e and 7 h exhibited weak inhibition against the spore germination of S. scleotiorum , while the spore germination of P. capsici was strongly inhibited by compound 7 h solution. Scanning electron microscopy (SEM ) and transmission electron microscopy (TEM ) observation indicated that compound 7 h had a significant impact on the structure and function of the hyphal cell wall of P. capsici mycelium.     

Diels‐alder reactions of 2‐(2‐nitroethenyl)‐1H‐pyrroles and their oxygen and sulfur analogs with quinones

Diels‐Alder reaction of 2‐(E‐2‐nitroethenyl)‐1H‐pyrrole ( 2a ) with 1,4‐benzoquinone gave the desired benzo[e]indole‐6, 9(3H)‐dione ( 4a ) in 10% yield versus a 26% yield (lit. 86% [5]) of the known N‐methyl compound ( 4b ) from the N‐(or 1)‐methyl compound ( 2b ). Protection of the nitrogen of 2a with a phenylsul‐fonyl group ( 2c ) gave a 9% yield of the corresponding N‐(or 3)‐phenylsulfonyl compound ( 4c ). The reaction of 2b with 1,4‐naphthoquinone gave in 6% yield (lit. 64% [5]) the known 3‐methylnaphtho[2,3‐e]‐indole‐6, 9(3H)‐dione ( 6 ). The reaction of 2‐(E‐2‐nitroethenyl)furan ( 8a ) gave a small yield of the desired naphtho[2,1‐b]furan‐6, 9‐dione ( 9a ), recognized by comparing its NMR spectrum with that of 4b. The corresponding reaction of 2‐(E‐2‐nitroethenyl)thiophene ( 8b ) gave a 4% yield of naphtho[2,1‐ b ]thiophene‐6,9‐dione ( 9b ), previously prepared in 24% yield [12] in a three‐step procedure involving 2‐ethenylthiophene. Introducing an electron‐releasing 2‐methyl substituent into 8a and 8b gave 12a and 12b , which, upon reaction with 1,4‐benzoquinone, gave 2‐methylnaphtho[2,1‐b]furan‐6, 9‐dione ( 13a ) and its sulfur analog ( 13b ) in yields of 4 and 8%, respectively.     

The Synthesis of 1,4‐Bis[N‐(4/6‐Substituted Benzothiazole‐2‐yl)‐N′‐Glycosylguanidino]Benzenes

The starting material O‐protected glycosyl isothiocyanate ( 1?3 ) was refluxed with 1,4‐diaminobenzene in CHCl₃ under nitrogen atmosphere to give 1,4‐bis(N‐glycosyl)thioureidobenzene ( 4?6 ). Then 1,4‐bis[N‐(4/6‐substituted benzothiazole‐2‐yl)‐N′‐glycosylguanidino]benzenes ( 8a?8e , 9a?9e , 10a?10e ) were obtained in good yield by reaction of compounds ( 4?6 ) with 2‐amino‐4/6‐benzothizoles ( 7a?7e ) and HgCl₂ in the presence of TEA in DMF. The structures of all 18 new compounds were confirmed by IR, ¹H NMR, LC‐MS and elemental analysis. The bioactivity of anti‐HIV‐1 protease (HIV‐1 PR) and against angiotensin converting enzyme (ACE) have been evaluated.     

An Efficient New Route for the Synthesis of Some 3‐Hterocyclylquinolinones via Novel 3‐(1,2‐Dihydro‐4‐hydroxy‐1‐methyl‐2‐oxoquinolin‐3‐yl)‐3‐oxopropanal and Their Antioxidant Screening

3‐(4‐hydroxy‐1‐methylquinoline‐3‐yl)‐3‐oxoproponal ( 5 ) was synthesized from 3‐[(E)‐3‐(dimethylamino)‐2‐propenoyl]‐4‐hydroxy‐1‐methyl‐2(1H )‐quinolinone ( 3 ) and was utilized as a starting precursor material. A convenient new route to functionalized 3‐heterocyclyl 4‐hydroxy‐2(1H )‐quinolinones such as pyrazolyl, isoxazolyl, pyrimidinyl, azepineyl , pyridonyl, and pyranyl heterocycles was described via cyclization of compound 5 with some N and C ‐nucleophiles. The newly synthesized aldehyde 5 showed only one ring closure possibility with maximum yield instead of using compound 3 that exhibited different regioselective ring closure routes with minimum yields. All newly synthesized products were structurally elucidated on the basis of their relevant spectroscopic data and elemental microanalyses. The antioxidant activity of the products was screened in a series of in vitro tests.     

Synthesis of benzo[c][1,8]phenanthrolin‐6‐one through cyclization of N‐(isoquinol‐5‐yl)‐2‐bromo‐benzamide derivatives

In the course of our search for compounds with potential antitumor properties we have undertaken the synthesis of benzo[c][1,8]phenanthroline derivatives. Our project required the preparation of 8,9‐dimethoxy benzo[c][1,8]phenanthrolin‐6‐ones. This was first attempted by the lithiumdiisopropylamide cyclization of N‐(isoquinol‐5‐yl)‐2‐bromo‐4,5‐dimethoxybenzamide. The reaction led to 40% of the unexpected internal Diels‐Alder adduct 3,4‐dimethoxy‐6H‐pyrido[2,3‐i]6,8a‐ethenoindolo[cd]isoquinoline‐2(1H)‐one, which arose from a benzyne intermediate. In a second and more successful approach, the internal biaryl palladium diacetate‐assisted coupling reaction of properly N‐protected N‐(isoquinol‐5‐yl)‐2‐bromo‐4,5‐dimethoxybenzamide was studied. The optimisation of the protecting group necessary for this procedure led to a 64% yield of the target compound starting from N,N‐(isoquinol‐5‐yl)‐bis‐(2‐bromo‐4,5‐dimethoxybenzamide).     

New Synthesis of 7‐(3‐chloropropoxy)‐4‐hydroxy‐6‐methoxyquinoline‐3‐carbonitrile,a Key Intermediate to Bosutinib

A new and convenient synthesis of 7‐(3‐chloropropoxy)‐4‐hydroxy‐6‐methoxyquinoline‐3‐carbonitrile, the key intermediate to bosutinib, is described on a hectogram scale. 5‐Bromo‐2‐methoxyphenol is adopted as the starting material via the simple chemical process including Friedel‐Crafts reaction, alkylation, bromination, cyano substitution, and so on to give the 3‐amino‐2‐(2‐bromobenzoyl)acrylonitrile compound 25 , which underwent key intramolecular cyclization at K₂CO₃/DMF condition; the title product was obtained in 36.9% yield over 7 steps and 98.71% purity (HPLC).