Total synthesis of oxyfagaronine, phenolic benzo[c]phenanthridine and general synthetic way of 2,3,7,8- and 2,3,8,9-tetrasubstituted benzo[c]phenanthridine alkaloids

Benzo[c]phenanthridine alkaloids such as oxynitidine, oxysanguinarine, oxyavicine and phenolic oxyfagaronine were synthesized from easily available starting benzonitriles 5 and toluamides 6 using a lithiated toluamide-benzonitrile cycloaddition reaction. The coupling reaction provided 3-arylisoquinolinones that were transformed to the benzo[c]phenanthridones. This method is highly efficient and could be useful for preparing diverse substituted aromatic benzo[c]phenanthridine compounds on a multi gram scale.     

Microwave‐Assisted Synthesis of Novel Spiro Phosphonyl Thiazolo Pyrazole Glycosides as Potential Nematicidal Agents

A series of novel dimethyl 7‐((3aR,5S,6S,6aR)‐6‐((1‐(4‐chlorophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)‐2,2‐dimethyltetrahydrofuro[2,3‐d][1,3]dioxol‐5‐yl)‐4‐(4‐fluorophenyl)‐9‐oxo‐8‐phenyl‐6‐thia‐1,2,8‐triazaspiro[4.4]non‐2‐en‐3‐ylphosphonate 2a – g were synthesized by the reaction of chalcone derivatives of 2‐((3aR,5S,6S,6aR)‐6‐((1‐(4‐chlorophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)‐2,2‐dimethyltetrahydrofuro[2,3‐d][1,3]dioxol‐5‐yl)‐3‐phenylthiazolidin‐4‐one 1 with Bestmann–Ohira reagent. The chemical structures of newly synthesized compounds were elucidated by IR, NMR, MS, and elemental analysis. The compounds 2a – g were evaluated for their nematicidal activity against Dietylenchus myceliophagus and Caenorhabditis elegans; compounds 2b , 2c , 2g , and 2f showed appreciable nematicidal activity.     

Naphthodioxinone‐1,3‐benzodioxole as photochemically masked one‐component type II photoinitiator for free radical polymerization

A 1,3‐benzodioxole derivative of naphthodioxinone, namely 2‐(benzo[d][1,3]dioxol‐5‐yl)‐9‐hydroxy‐2‐phenyl‐4H‐naphtho[2,3‐d][1,3]dioxin‐4‐one was synthesized and characterized. Its capability to act as caged one‐component Type II photoinitiator for free radical polymerization was examined. Upon irradiation, this photoinitiator releases 5‐benzoyl‐1,3‐benzodioxole possessing both benzophenone and 1,3‐dioxole groups in the structure as light absorbing and hydrogen donating sites, respectively. Subsequent photoexcitation of the benzophenone chromophore followed by hydrogen abstraction generates radicals capable of initiating free radical polymerization of appropriate monomers. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis of New Derivatives of 4‐(4,7,7‐Trimethyl‐7,8‐dihydro‐6H‐benzo[b]pyrimido[5,4‐e][1,4]thiazin‐2‐yl)morpholine

Cyclocondensation of 5‐amino‐6‐methyl‐2‐morpholinopyrimidine‐4‐thiol ( 1 ) and 2‐bromo‐5,5‐dimethylcyclohexane‐1,3‐dione ( 2 ) under mild reaction condition afforded 4,7,7‐trimethyl‐2‐morpholino‐7,8‐dihydro‐5H‐benzo[b ]pyrimido[5,4‐e ][1,4]thiazin‐9(6H )‐one ( 3 ). The ¹H and ¹³C NMR data of compound ( 3 ) are demonstrated that this compound exists primarily in the enamino ketone form. Reaction of compound ( 3 ) with phosphorous oxychloride gave 4‐(9‐chloro‐4,7,7‐trimethyl‐7,8‐dihydro‐6H‐benzo[b ]pyrimido[5,4‐e ][1,4]thiazin‐2‐yl)morpholine ( 4 ). Nucleophilic substitution of chlorine atom of compound ( 4 ) with typical secondary amines in DMF and K₂CO₃ furnished the new substituted derivatives of 4‐(4,7,7‐trimethyl‐7,8‐dihydro‐6H‐benzo[b ]pyrimido[5,4‐e ][1,4]thiazin‐2‐yl)morpholine ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h ). All the synthesized products were characterized and confirmed by their spectroscopic and microanalytical data.     

Microwave‐assisted Synthesis of Hybrid Heterocyclics as Biological Potent Molecules

A series of novel 5‐((1H‐benzo[d]imidazol‐2‐yl)methyl)‐2‐((3aR,5S,6S,6aR)‐2,2‐dimethyl‐6‐((1‐phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)tetrahydrofuro[2,3‐d][1,3]dioxol‐5‐yl)‐3‐phenylthiazolidin‐4‐ones 9a–n has been synthesized from triazole‐linked thiazolidinone derivatives 8a–g with o‐phenylenediamine and characterized by IR, NMR, MS, and elemental analyses. Further, these compounds were screened for their antibacterial activity against Gram‐positive bacteria, namely, Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538p), and Micrococcus luteus (IFC 12708), and Gram‐negative bacteria, namely, Proteus vulgaris (ATCC 3851), Salmonella typhimurium (ATCC 14028), and Escherichia coli (ATCC 25922). Among the screened compounds, compounds 9b , 9d , 9h , and 9i are highly active against almost all selected bacterial strains; the remaining compounds showed moderate to good activity and emerged as potential molecules for further development.     

A versatile total synthesis of benzo[c]phenanthridine and protoberberine alkaloids using lithiated toluamide-benzonitrile cycloaddition

A new versatile synthesis of benzo[c]phenanthridine and protoberberine alkaloids using lithiated toluamide-benzonitrile cycloaddition was carried out. The coupling reaction between benzonitrile 6 with o-toluamides (8a-c) afforded 3-arylisoquinolines (9a-c) that were transformed to the protoberberines (11a-c) or benzo[c]phenanthridines (14a-c). These compounds were synthesized by ring closure of the two-carbon chain on either position 2 or 4 of the 3-arylisoquinolinone (9a-c). Several kinds of substituted benzo[c]phenanthridine alkaloids such as oxysanguinarine, oxyavicine, and oxynitidine as well as protoberberines such as 8-oxocoptisine, 8-oxopseudoberberine, and 8-oxopseudocoptisine were synthesized.     

Synthesis of 2‐amino‐4‐(2‐ethoxybenzo[d][1,3]dioxol‐5‐yl)‐4H‐pyran‐3‐Carbonitrile Derivatives and Their Biological Evaluation

A new class of substituted 2‐amino‐4‐(2‐ethoxybenzo[d][1,3]dioxol‐5‐yl)‐4H‐pyran‐3‐carbonitrile derivatives catalyzed by Imidazole under mild reaction conditions has been developed. A variety of functionalized 2‐amino‐4‐(2‐ethoxybenzo[d][1,3]dioxol‐5‐yl)‐4H‐pyran‐3‐carbonitrile scaffolds were assembled in high yields by this catalytic protocol. The newly synthesized compounds have been characterized by IR, ¹H NMR, ¹³C NMR, and mass spectral data. The compounds were then evaluated for antimicrobial activities.     

Effective Synthesis of N‐Arylformamide from α‐Halo‐N‐arylacetamides

A convenient synthetic method for N‐arylformamide derivatives was successfully developed by reacting α‐iodo‐N‐arylacetamides with formamide. This method was applicable to α‐iodo‐N‐arylacetamide substrates bearing electron‐donating or electron‐withdrawing groups, N‐(benzo[d][1,3]dioxol‐5‐yl)‐2‐iodoacetamide, 2‐iodo‐N‐(pyridin‐2‐yl)acetamide, and 2‐iodo‐N‐(naphthalen‐4‐yl)acetamide to give the corresponding N‐arylformamides in moderate to excellent yields (65–94%). A plausible mechanism was proposed to account for the new transformation.     

A new approach for the synthesis of some pyrazolo[5,1‐c]triazines and pyrazolo[1,5‐a]pyrimidines containing naphtofuran moiety

Naphtho[2,1‐b]furan‐2‐yl)(8‐phenylpyrazolo[5,1‐c][1,2,4]triazin‐3‐yl)methanone, ([1,2,4]triazolo[3,4‐c][1,2,4]triazin‐6‐yl)(naphtho[2,1‐b]furan‐2‐yl)methanone, benzo[4,5]imidazo[2,1‐c][1,2,4]triazin‐3‐yl‐naphtho[2,1‐b]furan‐2‐yl‐methanone, 5‐(naphtho[2,1‐b]furan‐2‐yl)pyrazolo[1,5‐a]pyrimidine, 7‐(naphtho[2,1‐b]furan‐2‐yl)‐[1,2,4]triazolo[4,3‐a]pyrimidine, 2‐naphtho[2,1‐b]furan‐2‐yl‐benzo[4,5]imidazo[1,2‐a]pyrimidine, pyridine, and pyrazole derivatives are synthesized from sodium salt of 5‐hydroxy‐1‐naphtho[2,1‐b]furan‐2‐ylpropenone and various reagents. The newly synthesized compounds were elucidated by elemental analysis, spectral data, chemical transformation, and alternative synthetic route whenever possible. J. Heterocyclic Chem., (2012).     

Synthesis of 3‐(ω‐Hydroxyalkoxy)isobenzofuran‐1(3H)‐ones by Trifluoroacetic Acid‐Mediated Lactonization of tert‐Butyl 2‐(1,3‐Dioxol‐2‐yl)‐ or 2‐(1,3‐Dioxan‐2‐yl)benzoates

An efficient two‐step method for the preparation of 3‐(2‐hydroxyethoxy)‐ or 3‐(3‐hydroxypropoxy)isobenzofuran‐1(3H)‐ones 3 has been developed. Thus, the reaction of 1‐(1,3‐dioxol‐2‐yl)‐ or 1‐(1,3‐dioxan‐2‐yl)‐2‐lithiobenzenes, generated in situ by the treatment of 1‐bromo‐2‐(1,3‐dioxol‐2‐yl)‐ or 1‐bromo‐2‐(1,3‐dioxan‐2‐yl)benzenes 1 with BuLi in THF at ?78°, with (Boc)₂O afforded tert‐butyl 2‐(1,3‐dioxol‐2‐yl)‐ or 2‐(1,3‐dioxan‐2‐yl)benzoates 2 , which can subsequently undergo facile lactonization on treatment with CF₃COOH (TFA) in CH₂Cl₂ at 0° to give the desired products in reasonable yields.     

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).     

Crystallographic investigations of select cathinones: emerging illicit street drugs known as `bath salts'

The name `bath salts', for an emerging class of synthetic cathinones, is derived from an attempt to evade prosecution and law enforcement. These are truly illicit drugs that have psychoactive CNS (central nervous system) stimulant effects and they have seen a rise in abuse as recreational drugs in the last few years since first having been seen in Japan in 2006. The ease of synthesis and modification of specific functional groups of the parent cathinone make these drugs particularly difficult to regulate. MDPV (3,4‐methylenedioxypyrovalerone) is commonly encountered as its hydrochloride salt (C<sub>16</sub>H<sub>21</sub>NO<sub>3</sub>·HCl), in either the hydrated or the anhydrous forms. This `bath salt' has various names in the US, e.g. `Super Coke', `Cloud Nine', and `Ivory Wave', to name just a few. We report here the structures of two forms of the HCl salt, one as a mixed bromide/chloride salt, C<sub>16</sub>H<sub>22</sub>NO<sub>3</sub><sup>+</sup>·0.343Br<sup>−</sup>·0.657Cl<sup>−</sup> [systematic name: 1‐(benzo[d][1,3]dioxol‐5‐yl)‐2‐(pyrrolidin‐1‐ium‐1‐yl)pentan‐1‐one bromide/chloride (0.343/0.657)], and the other with the H<sub>7</sub>O<sub>3</sub><sup>+</sup> cation, as well as the HCl counter‐ion [systematic name: hydroxonium 1‐(benzo[d][1,3]dioxol‐5‐yl)‐2‐(pyrrolidin‐1‐ium‐1‐yl)pentan‐1‐one dichloride, H<sub>7</sub>O<sub>3</sub><sup>+</sup>·C<sub>16</sub>H<sub>22</sub>NO<sub>3</sub><sup>+</sup>·2Cl<sup>−</sup>]. This is one of a very few structures (11 to be exact) in which we have a new example of a precisely determined hydroxonium cation. During the course of researching the clandestine manufacture of MDPV, we were surprised by the fact that a common precursor of this illicit stimulant is known to be the fragrant species piperonal, which is present in the fragrances of orchids, most particularly in the case of the vanilla orchid. We found that MDPV can be made by a Grignard reaction of this heliotropin. This may also explain the unexpected appearance of the bromide counter‐ion in some of the salts we encountered (C<sub>16</sub>H<sub>21</sub>NO<sub>3</sub>·HBr), one of which is presented here [systematic name: 1‐(benzo[d][1,3]dioxol‐5‐yl)‐2‐(pyrrolidin‐1‐ium‐1‐yl)pentan‐1‐one bromide, C<sub>16</sub>H<sub>22</sub>NO<sub>3</sub><sup>+</sup>·Br<sup>−</sup>]. Complexation of MDPV with a forensic crystallizing reagent, HAuCl<sub>4</sub>, yields the tetrachloridoaurate salt of this drug, (C<sub>16</sub>H<sub>22</sub>NO<sub>3</sub>)[AuCl<sub>4</sub>]. The heavy‐metal complexing agent HAuCl<sub>4</sub> has been used for over a century to identify common quarternary nitrogen‐containing drugs via microscopic identification. Another street drug, called ethylone (3,4‐methylenedioxyethylcathinone), is regularly sold and abused as its hydrochloride salt (C<sub>12</sub>H<sub>15</sub>NO<sub>3</sub>·HCl), and its structure is herein described (systematic name: N‐{1‐[(benzo[d][1,3]dioxol‐5‐yl)carbonyl]ethyl}ethanaminium chloride, C<sub>12</sub>H<sub>16</sub>NO<sub>3</sub><sup>+</sup>·Cl<sup>−</sup>). Marketed and sold as a `bath salt', `plant feeder', or `cleaning product', this drug is nothing more than a slight chemical modification of the banned drug methylone (3,4‐methylenedioxymethcathinone). As with previously popular synthetic cathinones, the abuse of ethylone has seen a recent increase due to regulatory efforts on previous generations of cathinones that are now banned.     

Ring‐ring interconversions. Part 3. On the effect of the substituents on the thiazole moiety in the ring‐opening/ring‐closing reactions of nitrosoimidazo[2,1‐b][1,3]thiazoles with hydrochloric acid

The reaction of 6‐(4‐chlorophenyl)‐5‐nitrosoimidazo[2,1‐b][1,3]thiazole 1b , 6‐(4‐chlorophenyl)‐2‐methyl‐5‐nitrosoimidazo[2,1‐b][1,3]thiazole 1c , 6‐(4‐chlorophenyl)‐2,3‐dimethyl‐5‐nitrosoimidazo‐[2,1‐b][1,3]thiazole 1d and 2‐(4‐chlorophenyl)‐3‐nitrosobenzo[d]imidazo[2,1‐b][1,3]thiazole 1e with hydrochloric acid has been carried out in order to investigate the effect of substituents on the thiazole ring in a recently reported ring‐ring interconversion reaction. In every case the corresponding [1,4]‐thiazino[3,4‐c][1,2,4]oxadiazol‐3‐ones 2b‐e have been obtained. In particular, the benzoderivative 1e furnished the 4‐(4‐chlorophenyl)‐4‐hydroxy‐4H‐benzo[5,6][1,4]thiazino[3,4‐c][1,2,4]oxadiazol‐1‐one 2e , containing a new tricyclic system with a quasi‐planar geometry whose pharmacological potentialities appear promising.     

Syntheses of New Unsymmetrical 2,5‐Disubstituted‐1,3,4‐oxadiazoles and 1,2,4‐Triazolo[3,4‐b]‐1,3,4‐thiadiazoles Bearing Thieno[2,3‐c]pyrazolo Moiety

New series of (thieno[2,3‐c]pyrazolo‐5‐yl)‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazoles 10a , 10b , 10c and (thieno[2,3‐c]pyrazol‐5‐yl)‐1,3,4‐oxadiazol‐3(2H)‐yl)ethanones 6a , 6b , 6c has been synthesized from thieno[2,3‐c]pyrazole‐5‐carbohydrazide 3 by multistep reaction sequence. (5‐Aryl‐1,3,4‐oxadiazol‐2‐yl)‐1H‐thieno[2,3‐c]pyrazoles 4a , 4b , 4c were also synthesized from thieno[2,3‐c]pyrazole‐5‐carbohydrazide 3 by cyclization with various aromatic carboxylic acids. The hydrazide 3 was obtained by reaction of thieno[2,3‐c]pyrazole‐5‐carboxylate 2 with hydrazine hydrate in good yield, and compound 2 was obtained by the reaction of 5‐chloro‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde 1 and 2‐ethyl thioglycolate in presence of sodium alcoholate in good yield.     

Highly Efficient [3 + 2] Cycloaddition: Click Synthesis of Novel 1H‐indol‐3‐yl‐benzo[d]imidazole Bis‐triazoles

A series of novel 1‐((1H‐1,2,3‐triazol‐4‐yl)methyl)‐2‐(1‐((1H‐1,2,3‐triazol‐4‐yl)methyl)‐5‐substituted‐1H‐indol‐3‐yl)‐6‐substituted‐1H‐benzo[d]imidazoles 5a – i have been prepared using click chemistry as an ideal strategy where [3 + 2] cycloaddition of azides with terminal alkynes has been developed as the target compounds. In route‐II, 5‐substituted‐1H‐indole‐3‐carbaldehydes 1a – c react with 5‐substituted orthophenylenediamine 8 to give desired products, that is, 6‐substituted‐2‐(5‐substituted‐1H‐indol‐3‐yl)‐1H‐benzo[d]imidazole 6a – i . Here, 6a – i react with 2 equiv of propargylbromide 7 to give novel 6‐substituted 2‐(5‐substituted‐1‐(prop‐2‐yn‐1‐yl)‐1H‐indol‐3‐yl)‐1‐(prop‐2‐yn‐1‐yl)‐1H‐benzo[d]imidazole 4a – i . 4a – i were reacted with 2 equiv of NaN₃ in t‐butanol/water (1:2) and add catalytic amount of CuSO₄.5H₂O. Stir the reaction mixture at room temperature to get the target products 5a – i . Here, obtained products contain four rings, that is, one indole, two triazoles, and one benzimidazole. The main advantages of this method are short reaction times, easy workup, higher yields (88–92%), and no by‐products formation.     

Synthesis and Reactions of Some New Benzo[a]phenothiazine‐3,4‐dione Derivatives

The reaction of 2,3‐dihydro‐2,3‐epoxy‐1,4‐naphthoquinone ( 4 ) with substituted anilines furnished the corresponding benzo[fused]heterocyclic derivatives 5 , 6 , 6a , 6b , 7 , 8 . Furthermore, treatment of benzo[a]phenothiazine derivative 7 with halo compounds, namely, ethyl bromoacetate, phenacyl bromide, dibromoethane, or chloroacetone afforded ether derivatives 11 , 12 , 13 , 14 , respectively. Moreover, the reaction of 11 with o‐substituted aniline gave the corresponding benzo[a]phenothiazin‐5‐one derivatives 15 , 16 , 17 and benzo[d][1,3]oxazin‐4‐one 18 , respectively. Finally, the chromenone derivative 19 was synthesized via the reaction of ester derivative 11 with salicyaldhyde in refluxing pyridine. The newly synthesized compounds were characterized by spectroscopic measurements (IR, ¹H NMR, ¹³C NMR, and mass spectra).     

Synthesis of Heterocyclic Analogs of α‐aminoadipic Acid and its Esters Based on Imidazo[2,1‐b][1,3]Thiazole

A method for the preparation of heterocyclic analogs of α‐aminoadipic acid and its esters based on the imidazo[2,1‐b][1,3]thiazole ring system was developed. In this method, free‐radical bromination of ethyl 6‐methylimidazo[2,1‐b][1,3]thiazole‐5‐carboxylate with NBS afforded a versatile building block, ethyl 6‐bromomethylimidazo[2,1‐b][1,3]thiazole‐5‐carboxylate. Coupling of ethyl 6‐bromomethylimidazo[2,1‐b][1,3]thiazole‐5‐carboxylate with Schöllkopf's chiral auxiliary followed by acidic hydrolysis generated ethyl 6‐[(2S)‐2‐amino‐3‐methoxy‐3‐oxopropyl]imidazo[2,1‐b][1,3]thiazole‐5‐carboxylate. A similar procedure using diethyl (Boc‐amino)malonate yielded racemic 2‐amino‐3‐[(5‐ethoxycarbonyl)imidazo[2,1‐b][1,3]thiazol‐6‐yl]propanoic acid.     

Useful Precursors for Synthesis of Some New Azolo[3,4‐d]pyridiazines,Azolo[1,5‐a]pyrimidines,Azolo[5,1‐c]triazines,Pyrazoles, and Benzo[b][l,4]diazepine

Pyrazolo[3,4‐d]pyridazines, isoxazolo[3,4‐d]pyridazines, azolo[1,5‐a]pyrimidines, azolo[5,1‐c]triazines, pyrazoles, and benzo[b][l,4]diazepine were synthesized from the appropriate hydrazonoyl halides, hydroximoyl halides, heterocyclic amines, diazotized heterocyclic amines, arenediazonium chlorides, and o‐phenylenediamines with appropriate of sodium 3‐(5‐bromobenzofuran‐2‐yl)‐3‐oxoprop‐1‐en‐1‐olate or 1‐(5‐bromobenzofuran‐2‐yl)‐3‐(dimethylamino)prop‐2‐en‐1‐one. The newly synthesized compounds were elucidated by elemental analyses, spectral data, and alternative synthesis whenever possible.     

A facile synthesis of benzo[c]phenanthridine alkaloids: oxynitidine and oxysanguinarine using lithiated toluamide-benzonitrile cycloaddition

Benzo[c]phenanthridine alkaloids oxynitidine and oxysanguinarine were synthesized from easily available starting benzonitrile 5 and toluamide 6 using toluamide-benzonitrile cycloaddition reaction in six steps. This method is so highly efficient that it could be a more useful way for preparing fully aromatized benzo[c]phenanthridine compounds.     

Synthesis of Some New Pyridine and Pyrimidine Derivatives Containing Benzothiazole Moiety

A variety of pyridine and pyrimidine rings incorporating benzothiazole moiety were synthesized by reaction of 1‐(2‐benzothiazolyl)‐1‐cyano‐3‐chloroacetone ( 1 ) with 2‐pyridone, 2‐thioxopyridine, thiouracil, and 2‐thioxopyrimidine derivatives to give compounds 7,9‐dimethylfuro[2,3‐b:4,5‐b′]dipyridin‐4‐ol 5 , 4, 6‐diphenylthieno[2,3‐b]pyridin‐2‐yl 9 , 2‐(benzo[d]thiazol‐2‐yl)‐2‐(7‐substituted‐5‐oxo‐5H‐thiazolo[3,2‐a]pyrimidin‐3‐yl)acetonitriles 12a and 12b , pyrimido[2,1‐b][1,3]thiazepine‐3‐carboxamide 15 , and benzo[4,5]thiazolo[3,2‐b]pyridazine‐3‐one 20 , respectively.