- An integrated approach toward nanobret tracers for analysis of gpcr ligand engagement
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Gaining insight into the pharmacology of ligand engagement with G-protein coupled receptors (GPCRs) under biologically relevant conditions is vital to both drug discovery and basic research. NanoLuc-based bioluminescence resonance energy transfer (NanoBRET) monitoring competitive binding between fluorescent tracers and unmodified test compounds has emerged as a robust and sensitive method to quantify ligand engagement with specific GPCRs genetically fused to NanoLuc luciferase or the luminogenic HiBiT peptide. However, development of fluorescent tracers is often challenging and remains the principal bottleneck for this approach. One way to alleviate the burden of developing a specific tracer for each receptor is using promiscuous tracers, which is made possible by the intrinsic specificity of BRET. Here, we devised an integrated tracer discovery workflow that couples machine learning-guided in silico screening for scaffolds displaying promiscuous binding to GPCRs with a blend of synthetic strategies to rapidly generate multiple tracer candidates. Subsequently, these candidates were evaluated for binding in a NanoBRET ligand-engagement screen across a library of HiBiT-tagged GPCRs. Employing this workflow, we generated several promiscuous fluorescent tracers that can effectively engage multiple GPCRs, demonstrating the efficiency of this approach. We believe that this workflow has the potential to accelerate discovery of NanoBRET fluorescent tracers for GPCRs and other target classes.
- Boursier, Michelle E.,Hall, Mary P.,Hurst, Robin,Killoran, Michael P.,Kirkland, Thomas A.,Levin, Sergiy,Machleidt, Thomas,Ohana, Rachel Friedman,Zimmerman, Kristopher
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- Mild deprotection of the: N-tert -butyloxycarbonyl (N -Boc) group using oxalyl chloride
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We report a mild method for the selective deprotection of the N-Boc group from a structurally diverse set of compounds, encompassing aliphatic, aromatic, and heterocyclic substrates by using oxalyl chloride in methanol. The reactions take place under room temperature conditions for 1-4 h with yields up to 90percent. This mild procedure was applied to a hybrid, medicinally active compound FC1, which is a novel dual inhibitor of IDO1 and DNA Pol gamma. A broader mechanism involving the electrophilic character of oxalyl chloride is postulated for this deprotection strategy. This journal is
- Awuah, Samuel G.,George, Nathaniel,Ofori, Samuel,Parkin, Sean
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p. 24017 - 24026
(2020/07/23)
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- Leveraging a Low-Affinity Diazaspiro Orthosteric Fragment to Reduce Dopamine D3 Receptor (D3R) Ligand Promiscuity across Highly Conserved Aminergic G-Protein-Coupled Receptors (GPCRs)
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Previously, we reported a 3-(2-methoxyphenyl)-9-(3-((4-methyl-5-phenyl-4H-1,2,4-triazol-3-yl)thio)propyl)-3,9-diazaspiro[5.5]undecane (1) compound with excellent dopamine D3 receptor (D3R) affinity (D3R Ki = 12.0 nM) and selectivity (D2R/D3R ratio = 905). Herein, we present derivatives of 1 with comparable D3R affinity (32, D3R Ki = 3.2 nM, D2R/D3R ratio = 60) and selectivity (30, D3R Ki = 21.0 nM, D2R/D3R ratio = 934). Fragmentation of 1 revealed orthosteric fragment 5a to express an unusually low D3R affinity (Ki = 2.7 μM). Compared to piperazine congener 31, which retains a high-affinity orthosteric fragment (5d, D3R Ki = 23.9 nM), 1 was found to be more selective for the D3R among D1- and D2-like receptors and exhibited negligible off-target interactions at serotoninergic and adrenergic G-protein-coupled receptors (GPCRs), common off-target sites for piperazine-containing D3R scaffolds. This study provides a unique rationale for implementing weakly potent orthosteric fragments into D3R ligand systems to minimize drug promiscuity at other aminergic GPCR sites.
- Reilly, Sean W.,Riad, Aladdin A.,Hsieh, Chia-Ju,Sahlholm, Kristoffer,Jacome, Daniel A.,Griffin, Suzy,Taylor, Michelle,Weng, Chi-Chang,Xu, Kuiying,Kirschner, Nathan,Luedtke, Robert R.,Parry, Christopher,Malhotra, Shipra,Karanicolas, John,Mach, Robert H.
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p. 5132 - 5147
(2019/05/28)
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- Mixed er-NHC/phosphine Pd(ii) complexes and their catalytic activity in the Buchwald-Hartwig reaction under solvent-free conditions
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A series of novel (NHC)PdCl2-PR3 complexes were synthesized and fully characterized by 1H, 13C, 31P NMR and FT-IR spectroscopy. These complexes showed high catalytic activity toward solvent-free Buchwald-Hartwig amination. Both primary and secondary amines were efficiently utilized under the same reaction conditions. The solvent-free synthesis of valuable N-aryl carbazoles and similar N-heterocyclic systems was described.
- Ageshina, Alexandra A.,Sterligov, Grigorii K.,Rzhevskiy, Sergey A.,Topchiy, Maxim A.,Chesnokov, Gleb A.,Gribanov, Pavel S.,Nechaev, Mikhail S.,Asachenko, Andrey F.,Bermeshev, Maxim V.,Melnikova, Elizaveta K.
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supporting information
p. 3447 - 3452
(2019/04/30)
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- 5-[3-[PIPERAZIN-1-YL]-3-OXO-PROPYL]-IMIDAZOLIDINE-2,4-DIONE DERIVATIVES AS ADAMTS 4 AND 5 INHIBITORS FOR TREATING E.G. OSTEOARTHRITIS
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The present invention discloses 5-[3-[piperazin-l-yl]-3-oxo-propyl]-imidazolidine-2,4-dione derivatives according to Formula (I), wherein R1, R2, R3a, R3b, R6a, R6b, the subscript n and Cy are as defined herein. The present invention relates to compounds inhibiting ADAMTS 4 and 5 for the prophylaxis or treatment of inflammatory diseases or diseases involving degradation of cartilage or disruption of cartilage homeostasis, such as e.g. osteoarthritis.
- -
-
Paragraph 0219; 0304
(2018/01/15)
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- Development of a Unique Heterogeneous Palladium Catalyst for the Suzuki–Miyaura Reaction using (Hetero)aryl Chlorides and Chemoselective Hydrogenation
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A unique heterogeneous palladium catalyst (7% Pd/WA30) supported on an anion exchange resin, which contains N,N-dimethylaminoalkyl functionalities on the polymer backbone, was developed. 7% Pd/WA30 could smoothly catalyze Suzuki–Miyaura reactions of even less reactive heteroaryl chlorides and heteroarylboronic acids to afford various (hetero)biaryls due to the electron-donating effect of the tert-amines on WA30 to Pd species. It was also applicable as a chemoselective hydrogenation catalyst, showing inactivity for the hydrogenolysis of tert-butyldimethylsilyl (TBS) ethers, alkyl benzyl ethers, and benzyl alcohols. The tert-amines on WA30 acted as moderate catalyst poisons for Pd, resulting in chemoselective hydrogenation. 7% Pd/WA30 was reused for at least five times without any loss of the hydrogenation catalytic activity. (Figure presented.).
- Ichikawa, Tomohiro,Netsu, Moeko,Mizuno, Masahiro,Mizusaki, Tomoteru,Takagi, Yukio,Sawama, Yoshinari,Monguchi, Yasunari,Sajiki, Hironao
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supporting information
p. 2269 - 2279
(2017/07/07)
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- Highly Selective Dopamine D3 Receptor Antagonists with Arylated Diazaspiro Alkane Cores
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A series of potent and selective D3 receptor (D3R) analogues with diazaspiro alkane cores were synthesized. Radioligand binding of compounds 11, 14, 15a, and 15c revealed favorable D3R affinity (Ki = 12-25.6 nM) and were highly selective for D3R vs D3R (ranging from 264- to 905-fold). Variation of these novel ligand architectures can be achieved using our previously reported 10-20 min benchtop C-N cross-coupling methodology, affording a broad range of arylated diazaspiro precursors.
- Reilly, Sean W.,Griffin, Suzy,Taylor, Michelle,Sahlholm, Kristoffer,Weng, Chi-Chang,Xu, Kuiying,Jacome, Daniel A.,Luedtke, Robert R.,Mach, Robert H.
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p. 9905 - 9910
(2017/12/26)
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- Charge-transfer-directed radical substitution enables para-selective C-H functionalization
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Efficient C-H functionalization requires selectivity for specific C-H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho and meta selectivity, but a general strategy for para-selective C-H functionalization has remained elusive. Herein we introduce a previously unappreciated concept that enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit arene-to-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate with a simple theoretical tool that the selectivity is predictable and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of radical substitution directed by charge transfer could serve as the basis for the development of new, highly selective C-H functionalization reactions.
- Boursalian, Gregory B.,Ham, Won Seok,Mazzotti, Anthony R.,Ritter, Tobias
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p. 810 - 815
(2016/07/29)
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- Identification of novel GLUT inhibitors
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The compound class of 1H-pyrazolo[3,4-d]pyrimidines was identified using HTS as very potent inhibitors of facilitated glucose transporter 1 (GLUT1). Extensive structure–activity relationship studies (SAR) of each ring system of the molecular framework was established revealing essential structural motives (i.e., ortho-methoxy substituted benzene, piperazine and pyrimidine). The selectivity against GLUT2 was excellent and initial in vitro and in vivo pharmacokinetic (PK) studies are encouraging.
- Siebeneicher, Holger,Bauser, Marcus,Buchmann, Bernd,Heisler, Iring,Müller, Thomas,Neuhaus, Roland,Rehwinkel, Hartmut,Telser, Joachim,Zorn, Ludwig
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p. 1732 - 1737
(2016/07/27)
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- Pd-Catalyzed Synthesis of Piperazine Scaffolds under Aerobic and Solvent-Free Conditions
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A facile Pd-catalyzed methodology providing an efficient synthetic route to biologically relevant arylpiperazines under aerobic conditions is reported. Electron donating and sterically hindered aryl chlorides were aminated to afford yields up to 97%, with examples using piperazine as solvent, illustrating an ecofriendly, cost-effective synthesis of these privileged structures.
- Reilly, Sean W.,Mach, Robert H.
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supporting information
p. 5272 - 5275
(2016/10/31)
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- Structural modifications of neuroprotective anti-parkinsonian (-)-N6-(2-(4-(biphenyl-4-yl)piperazin-1-yl)-ethyl)-N6-propyl-4,5,6, 7-tetrahydrobenzo[d]thiazole-2,6-diamine (D-264): An effort toward the improvement of in vivo efficacy of the parent molecule
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In our overall goal to develop multifunctional dopamine D 2/D3 agonist drugs for the treatment of Parkinson's disease (PD), we previously synthesized potent D3 preferring agonist D-264 (1a), which exhibited neuroprotective properties in two animal models of PD. To enhance the in vivo efficacy of 1a, a structure-activity relationship study was carried out. Competitive binding and [35S]GTPγS functional assays identified compound (-)-9b as one of the lead molecules with preferential D3 agonist activity (EC50(GTPγS); D3 = 0.10 nM; D2/D3 (EC50): 159). Compounds (-)-9b and (-)-8b exhibited high in vivo activity in two PD animal models, reserpinized and 6-hydroxydopamine (OHDA)-induced unilateral lesioned rats. On the other hand, 1a failed to show any in vivo activity in these models unless the compound was dissolved in 5-10% beta-hydroxy propyl cyclodextrin solution. Lead compounds exhibited appreciable radical scavenging activity. In vitro experiments with dopaminergic MN9D cells indicated neuroprotection by both 1a and (-)-9b from toxicity of MPP+.
- Modi, Gyan,Antonio, Tamara,Reith, Maarten,Dutta, Aloke
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p. 1557 - 1572
(2014/03/21)
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- FUNCTIONALLY SELECTIVE LIGANDS OF DOPAMINE D2 RECEPTORS
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The present invention relates to novel functionally selective ligands of dopamine D2 receptors, including agonists, antagonists, and inverse agonists. The invention further relates to the use of these compounds for treating central nervous system disorders related to D2 receptors.
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Page/Page column 105
(2012/01/15)
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- THERAPEUTICALLY ACTIVE COMPOUNDS FOR USE IN THE TREATMENT OF CANCER CHARACTERIZED AS HAVING AN IDH MUTATION
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Compounds and compositions comprising compounds useful in the treatment of cancer are described herein. The compounds and compositions can be used to modulate an isocitrate dehydrogenase (IDH) mutant (e.g., IDHIm or IDH2m) having alpha hydroxyl neoactivity
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Page/Page column 107
(2011/06/26)
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- A simple and efficient asymmetric synthesis of anxiolytic drug enciprazine
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A straightforward and efficient asymmetric synthesis of (S)-1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(3,4,5-trimethoxyphenoxy) propan-2-ol is described. The key intermediate, (S)-2-[(3,4,5-trimethoxyphenoxy) methyl]oxirane, was obtained by a hydrolytic kinetic resolution method using the catalyst (R,R)-salen-cobalt(III) complex. Georg Thieme Verlag Stuttgart.
- Narsaiah, A. Venkat,Nagaiah
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experimental part
p. 2705 - 2707
(2010/10/18)
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- Zinc(II) perchlorate hexahydrate catalyzed opening of epoxide ring by amines: Applications to synthesis of (RS)/(R)-propranolols and (RS)/(R)/(S)-naftopidils
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(Figure Presented) Commercially available zinc(II) Perchlorate hexahydrate [Zn(ClO4)2·6H2O] was found to be a new and highly efficient catalyst for opening of epoxide rings by amines affording 2-amino alcohols in high yields under solvent-free conditions and with excellent chemo-, regio-, and stereoselectivities. For unsymmetrical epoxides, the regioselectivity was influenced by the electronic and steric factors associated with the epoxides and the amines. A complementarity in the regioselectivity was observed during the reaction of styrene oxide with aromatic and aliphatic amines: aromatic amines provided amino alcohols from nucleophilic attack at the benzylic carbon as major products whereas aliphatic amines resulted in formation of the amino alcohols through reaction at the terminal carbon atom of the epoxide ring as the major/sole products. Reaction of aniline with various glycidic ethers gave the amino alcohols by regioselective nucleophilic attack at the terminal carbon atom of the epoxide ring as the only/major product. Zinc(II) Perchlorate hexahydrate was found to be the best catalyst compared to other metal Perchlorates. The counteranion modulated the catalytic property of the various Zn(II) compounds that followed the order Zn(ClO4) 2·6H2O Zn(BF4)2 ～ Zn(OTf)2 ZnI2 > ZnBr2 > ZnCl2 > Zn(OAc)2 > Zn(CO3)2 in parallelism with the acidic strength of the corresponding protic acids (except for TfOH). The applicability of the methodology was demonstrated by the synthesis of cardiovascular drugs propranolol and naftopidil as racemates and optically active enantiomers.
- Shivani,Pujala, Brahmam,Chakraborti, Asit K.
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p. 3713 - 3722
(2008/02/05)
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- ADRENERGIC RECEPTOR ANTAGONISTS
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The present invention relates to α1a and/or α1b adrenergic receptor antagonists, which can be used to treat a disease or disorder mediated through α1a and/or α1b adrenergic receptors. Compounds and pharmaceutical compositions disclosed herein can be used to treat benign prostatic hyperplasia (BPH) and related symptoms thereof. Further, such compounds can be used to treat lower urinary tract symptoms that may or may not be associated with BPH. The present invention also relates to processes to prepare the disclosed compounds, pharmaceutical compositions thereof, and methods of treating BPH or related symptoms thereof.
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Page/Page column 50
(2010/11/24)
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- Hydrolytic kinetic resolution of α-naphthyl glycidyl ether: A practical access to highly enantioselective β-adrenergic blocking agents
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Kinetic resolution of (±)-naphthyl glycidyl ether using 0.5 mol% (R,R)-salen Co(III)OAc and water (0.55 equiv) provided enantiomerically pure naphthyl glycidyl ether and 1-naphthylglycerol derivatives with high enantiomeric excess. Application of this approach to highly enantioenriched (S)-naftopidil and (S)-propranolol is described. Georg Thieme Verlag Stuttgart.
- Subhas Bose,Narsimha Reddy,Chavhan, Sanjay W.
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p. 2345 - 2348
(2007/10/03)
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- SEROTONIN REUPTAKE INHIBITORS
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A serotonin reuptake inhibitor which can be used in the treatment of depression and which has a decreased occurrence of unwanted side effects. The serotonin reuptake inhibitors are bi-functional organic molecules which combine serotonin transporter reuptake inhibition with serotonin (5-HT,such as 5-HT2A) receptor antagonism in one molecular entity. The serotonin-selective reuptake inhibitor (SSRI) homologue portion of the molecule shows an affinity to the serotonin reuptake transporter (SERT) and has antidepressant properties. The piperazine or piperidine portion of the molecule demonstrates an affinity to 5-HT receptors and restores the undesired side effects of SSRIs.
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Page/Page column 21
(2010/02/14)
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- Arylpiperazines having activity at the serotonin 1A receptor
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A series of aryl piperazine compounds are effective pharmaceuticals for the treatment of conditions related to or affected by the serotonin 1A receptor; the compounds are particularly effective antagonists at that receptor, and are particularly useful for alleviating the symptoms of nicotine and tobacco withdrawal.
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- The first enantiomerically pure synthesis of (S)- And (R)-naftopidil utilizing hydrolytic kinetic resolution of (±)-(α-Naphthyl) glycidyl ether
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Hydrolytic Kinetic Resolution (HKR) of (±)-(α-Naphthyl) glycidyl ether with (R,R)-salen Co(III) OAc complex provided enatiomerically pure (S)-naphthyl glycidyl ether and (R)-1-naphthyl glycerol; opening of the corresponding pure terminal epoxide with 1-(2-methoxyphenyl)piperizine gave the enantiomerically pure (S)- and (R)-Naftopidil.
- Kothakonda, Kiran Kumar,Bose, D. Subhas
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p. 1212 - 1213
(2007/10/03)
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- Mono N-arylation of piperazine(III): Metal-catalyzed N-arylation and its application to the novel preparations of the antifungal posaconazole and its advanced intermediate
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A novel application of Pd0-catalyzed arylation to mono N-arylated piperazines, its mechanism, and its application towards the novel syntheses of the key differentially N,N′-diarylated piperazine antifungal intermediate N-(4-hydroxyphenyl)-N′-(4-aminophenyl)piperazine 5 as well as posaconazole 1 are described.
- Hepperle, Michael,Eckert, Jeffrey,Gala, Dinesh,Shen, Lan,Anderson Evans,Goodman, Andrew
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p. 3359 - 3363
(2007/10/03)
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- Fused heterocyclic compounds and pharmaceutical applications thereof
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The present invention relates to a fused heterocyclic compound of the formula (I) wherein each symbol is as defined in the specification, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing a compound of the formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive, and a medicament containing a compound of the formula (I), an optical isomer thereof or a pharmaceutically acceptable salt thereof. The compound of the present invention is a useful antipsychotic agent effective not only for positive symptoms centering on hallucination and delusion characteristic of the acute stage of schizophrenia, but also negative symptoms of apathy, abulia and autism. The inventive compound is expected to make a highly safe antipsychotic agent associated with less side effects, such as extrapyramidal symptoms and endocrine disturbance, which are observed when a conventional antipsychotic agent having a D2receptor blocking action is administered. Therefore, the inventive compound can be used as a therapeutic agent for the diseases such as schizophrenia.
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-
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- Arylpiperazines having activity at the serotonin 1A receptor
-
A series of aryl piperazine compounds of the formula: or the pharmaceutically acceptable salts thereof, are effective pharmaceuticals for the treatment of conditions related to or affected by the serotonin 1Areceptor; the compounds are particularly effective antagonists at that receptor, and are particularly useful for alleviating the symptoms of nicotine and tobacco withdrawal.
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-
- Synthesis of potent and selective dopamine D4 antagonists as candidate radioligands
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A series of dopamine D4 antagonists was synthesized and evaluated as potential candidates for development as positron emission tomography (PET) radioligands. All new compounds display high affinity and selectivity for the D4 receptors and compounds 5b, 5d, and 5e were identified as candidates for radioligand development.
- Huang, Yiyun,Kegeles, Lawrence S.,Bae, Sung-A,Hwang, Dah-ren,Roth, Bryan L.,Savage, Jason E.,Laruelle, Marc
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p. 1375 - 1377
(2007/10/03)
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- Process for producing heterocyclic aromatic amine or arylamine
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A heterocyclic aromatic halide or an aryl halide is reacted with an amine compound in the presence of a base to give a heterocyclic aromatic amine or an arylamine, respectively. In this reaction, a catalyst comprising a palladium compound and a tertiary phosphine is used for the preparation of a heterocyclic aromatic amine, and a catalyst comprising a palladium compound and a trialkylphosphine is used for the preparation of an arylamine.
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- Scavenger assisted combinatorial process for preparing libraries of amides, carbamates and sulfonamides
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This invention relates to a novel solution phase process for the preparation of amide, carbamate, and sulfonamide combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
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- Synthesis of N-arylpiperazines from aryl halides and piperazine under a palladium tri-tert-butylphosphine catalyst
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A Pd/P(t-Bu), catalyst system has revealed very high activity and selectivity for the amination of N-(hetero)aryl halides with unprotected piperazine. A wide variety of N-(hetero)arylpiperazines could be prepared using this catalyst. Turnover numbers up to 6400mol/mol have been obtained.
- Nishiyama, Masakazu,Yamamoto, Toshihide,Koie, Yasuyuki
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p. 617 - 620
(2007/10/03)
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- Synthesis of arylpiperazines via nucleophilic aromatic substitution of (η6-fluoroarene)tricarbonylchromium complexes
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A one-pot, high yield preparation procedure for the synthesis of arylpiperazines using a nucleophilic aromatic substitution of (η6-fluoroarene)tricarbonylchromium complexes (including those bearing electron donating groups) is described. A new, easy and fast decomplexation procedure, in DMSO as solvent, is also presented.
- Perez, Michel,Potier, Pierre,Halazy, Serge
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p. 8487 - 8488
(2007/10/03)
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- Antiviral agents
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Antiviral compounds (I): the symbols being as defined in the specification, are efficacious against infections caused by a variety of DNA viruses, RNA viruses and retroviruses. Other specified compounds also exhibit activity. The compounds have a wider spectrum of activity than known antiviral substances.
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- Direct Substitution of Aromatic Ethers by Lithium Amides. A New Aromatic Amination Reaction
-
Reaction of lithiated dialkylamines with methoxy aromatics in refluxing THF leads to products resulting from a direct ipso-substitution.Especially with lithiated secondary amines high conversions and selectivities are achieved.Sulfonyl-substituted aromatics react equally well, but halogenated aromatics give rise to side-products arising from a competing pathway via aryne intermediates.The scope and mechanistic implications of this novel nucleophilic amination reaction are described.
- Hoeve, Wolter ten,Kruse, Chris, G.,Luteyn, Jan M.,Thiecke, Janet R. G.,Wynberg, Hans
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p. 5101 - 5106
(2007/10/02)
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- POTENTIAL NEUROLEPTICS OF THE ORTHOPRAMIDE SERIES; SYNTHESIS OF N-(3-(TERT.AMINO)PROPYL)-5-SULFAMOYL-2-METHOXYBENZAMIDES
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Heating ethyl 5-sulfamoyl-2-methoxybenzoate with a series of twelve 3-(tert.amino)propylamines (IIIa-IIIl) afforded the title compounds IIa-IIl which were transformed to salts and subjected to pharmacological screening as potential neuroleptics of the sulpiride series.Only compounds IId (hydrogen oxalate, VUFB-15 453) and IIg (methanesulfonate, VUFB-15 397) showed indications of the desired psychotropic activity.
- Valenta, Vladimir,Vlkova, Marie,Holubek, Jiri,Svatek, Emil,Metysova, Jirina,Protiva, Miroslav
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p. 797 - 808
(2007/10/02)
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- Single-step conversion of aliphatic, aromatic and heteroaromatic primary amines into piperazine-2,6-diones
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The development of a facile, single-step method for the synthesis of 1,4-disubstituted piperazine-2,6-diones (4) in excellent yields from the corresponding aliphatic, aromatic and heteroaromatic primary amines and iminodiacetic acids (1) is described.A possible mechanism is discussed and the presence of intermediate 6a is confirmed by high-resolution proton NMR spectroscopy.The subsequent two-step conversion of dione 4a into the deoxygenated 4-unsubstituted piperazine 10 in high yield provides an attractive alternative to the currently available (hetero)arylpiperazine synthetic methods.
- Kruse, C. G.,Troost, J. J.,Cohen-Fernandes, P.,Linden, H. van der,Loon, J. D. van
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p. 303 - 310
(2007/10/02)
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