Heterocyclic Building Blocks-piperidine

Borodkin, G. I. published the artcileReaction of Nitrosonium Tetrafluoroborate with Nitroxyl Radicals, Name: 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, the publication is Russian Journal of Organic Chemistry (Translation of Zhurnal Organicheskoi Khimii) (2003), 39(8), 1144-1150, database is CAplus.

It was established by means of multinuclear magnetic resonance method (¹H, ¹³C, ¹⁹F and ¹⁴N) that reaction of 2,2,6,6-tetramethyl-4-R-piperidin-1-oxyl radicals (R = H, OH, OMe, OCOPh, NHCOMe) with nitrosonium tetrafluoroborate gave rise to the corresponding 2,2,6,6-tetramethyl-1-oxo-4-R-piperidinium tetrafluoroborates. Linear correlations were found between the chem. shifts of atoms H⁴, C⁴ of cations and resp. σ₁-constants of substituents R and chem. shifts of C⁴ atom calculated from increments of substitution. The conformational features of the generated nitrosonium cations are considered on the grounds of vicinal coupling constants J_HH and quantum-chem. calculations by AM1 method.

Russian Journal of Organic Chemistry (Translation of Zhurnal Organicheskoi Khimii) published new progress about 219543-09-6. 219543-09-6 belongs to piperidines, auxiliary class Piperidine,Fluoride,Salt,Amine,Amide, name is 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, and the molecular formula is C11H21BF4N2O2, Name: 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Bobbitt, James M. published the artcileDiscussion addendum for: preparation of 4-acetylamino-2,2,6,6-tetramethylpiperidine-1- oxoammonium tetrafluoroborate and the oxidation of geraniol to geranial (2,6-octadienal, 3,7-dimethyl-, (2e)-), Application In Synthesis of 219543-09-6, the publication is Organic Syntheses (2013), 215-228, database is CAplus.

A review. Addendum to an original article published by Bobbitt, J. M. and Merbouh, N. in Organic Synth. 2005, 82, 80. Revised preparations of I and II•BF₄^–, their solubility properties and relevance in stoichiometric alc. oxidation reactions, and examples of selective alc. oxidations of polyalcs. as well as other recent developments were discussed.

Organic Syntheses published new progress about 219543-09-6. 219543-09-6 belongs to piperidines, auxiliary class Piperidine,Fluoride,Salt,Amine,Amide, name is 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, and the molecular formula is C11H21BF4N2O2, Application In Synthesis of 219543-09-6.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Bobbitt, James M. published the artcilePreparation of Some Homologous TEMPO Nitroxides and Oxoammonium Salts; Notes on the NMR Spectroscopy of Nitroxide Free Radicals; Observed Radical Nature of Oxoammonium Salt Solutions Containing Trace Amounts of Corresponding Nitroxides in an Equilibrium Relationship, Product Details of C11H21BF4N2O2, the publication is Journal of Organic Chemistry (2017), 82(18), 9279-9290, database is CAplus and MEDLINE.

Three new homologous TEMPO oxoammonium salts and three homologous nitroxide radicals have been prepared and characterized. The oxidation properties of the salts have been explored. The direct ¹³C NMR and EPR spectra of the nitroxide free radicals and the oxoammonium salts, along with TEMPO and its oxoammonium salt, have been successfully measured with little peak broadening of the NMR signals. In the spectra of all ten compounds (nitroxides and corresponding oxoammonium salts), the carbons in the 2,2,6,6-tetramethylpiperidine core do not appear, implying paramagnetic properties. This unpredicted overall paramagnetism in the oxoammonium salt solutions is explained by a redox equilibrium as shown between oxoammonium salts and trace amounts of corresponding nitroxide. This equilibrium is confirmed by electron interchange reactions between nitroxides with an N-acetyl substituent and oxoammonium salts with longer acyl side chains.

Journal of Organic Chemistry published new progress about 219543-09-6. 219543-09-6 belongs to piperidines, auxiliary class Piperidine,Fluoride,Salt,Amine,Amide, name is 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, and the molecular formula is C11H21BF4N2O2, Product Details of C11H21BF4N2O2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Gholivand, Khodayar published the artcileSynthesis, biological evaluation, QSAR study and molecular docking of novel N-(4-amino carbonylpiperazinyl) (thio)phosphoramide derivatives as cholinesterase inhibitors, Synthetic Route of 39546-32-2, the publication is Pesticide Biochemistry and Physiology (2014), 40-50, database is CAplus and MEDLINE.

Novel (thio)phosphoramidate derivatives based on piperidincarboxamide with the general formula of (NH₂-C(O)-C₅H₉N)-P(X = O,S)R₁R₂ (1-5) and (NH₂-C(O)-C₅H₉N)₂-P(O)R (6-9) were synthesized and characterized by ³¹P, ¹³C, ¹H NMR, IR spectroscopy. Furthermore, the crystal structure of compound (NH₂-C(O)-C₅H₉N)₂-P(O)(OC₆H₅) (6) was investigated. The activities of derivatives on cholinesterases (ChE) were determined using a modified Ellman’s method. Also the mixed-type mechanisms of these compounds were evaluated by Lineweaver-Burk plots. Mol. docking and quant. structure-activity relationship (QSAR) were used to understand the relationship between mol. structural features and anti-ChE activity, and to predict the binding affinity of phosphoramido-piperidinecarboxamides (PAPCAs) to ChE receptors. From mol. docking anal., noncovalent interactions especially hydrogen bonding as well as hydrophobic was found between PAPCAs and ChE. Based on the docking results, appropriate mol. structural parameters were adopted to develop a QSAR model. DFT-QSAR models for ChE enzymes demonstrated the importance of electrophilicity parameter in describing the anti-AChE and anti-BChE activities of the synthesized compounds The correlation matrix of QSAR models and docking anal. confirmed that electrophilicity descriptor can control the influence of the hydrophobic properties of P = (O, S) and C=O functional groups of PAPCA derivatives in the inhibition of human ChE enzymes.

Pesticide Biochemistry and Physiology published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Synthetic Route of 39546-32-2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Wang, Tao published the artcileA New Synthetic Route to Avibactam: Lipase Catalytic Resolution and the Simultaneous Debenzylation/Sulfation, Quality Control of 1416134-49-0, the publication is Organic Process Research & Development (2018), 22(3), 267-272, database is CAplus.

An efficient synthesis of avibactam starting from com. available ethyl-5-hydroxypicolinate was completed in ten steps and 23.9% overall yield. The synthesis features a novel lipase-catalyzed resolution, in the preparation of (2S,5S)-5-hydroxypiperidine-2-carboxylate acid, which are valuable precursors of the key intermediate Et (2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxylate. An optimized one-pot debenzylation / sulfation reaction, followed by cation exchange, gave the avibactam sodium salt on a 400.0 g scale.

Organic Process Research & Development published new progress about 1416134-49-0. 1416134-49-0 belongs to piperidines, auxiliary class Piperidine,Chiral,Amine,Benzene,Amide, name is (2S,5R)-5-((Benzyloxy)amino)piperidine-2-carboxamide, and the molecular formula is C15H21BO2, Quality Control of 1416134-49-0.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Wang, Tao published the artcileUse of Lipase Catalytic Resolution in the Preparation of Ethyl (2S,5R)-5-((Benzyloxy)amino)piperidine-2-carboxylate, a Key Intermediate of the β-Lactamase Inhibitor Avibactam, Computed Properties of 1416134-49-0, the publication is Organic Process Research & Development (2018), 22(12), 1738-1744, database is CAplus.

Here we describe an efficient and cost-effective chemoenzymic synthesis of the β-lactamase inhibitor avibactam starting from com. available Et 5-hydroxypicolinate hydrochloride. Avibactam was synthesized in 10 steps with an overall yield of 23.9%. The synthetic route features a novel lipase-catalyzed resolution step during the preparation of (2S,5S)-Et 5-hydroxypiperidine-2-carboxylate, a valuable precursor of the key intermediate Et (2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxylate. Our synthetic route was used to produce 400 g of avibactam sodium salt.

Organic Process Research & Development published new progress about 1416134-49-0. 1416134-49-0 belongs to piperidines, auxiliary class Piperidine,Chiral,Amine,Benzene,Amide, name is (2S,5R)-5-((Benzyloxy)amino)piperidine-2-carboxamide, and the molecular formula is C15H21BO3, Computed Properties of 1416134-49-0.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Bryan, Marian C. published the artcileDevelopment of Potent and Selective Pyrazolopyrimidine IRAK4 Inhibitors, Application of Piperidine-4-carboxamide, the publication is Journal of Medicinal Chemistry (2019), 62(13), 6223-6240, database is CAplus and MEDLINE.

A series of pyrazolopyrimidine inhibitors of IRAK4 were developed from a high-throughput screen (HTS). Modification of an HTS hit led to a series of bicyclic heterocycles with improved potency and kinase selectivity but lacking sufficient solubility to progress in vivo. Structure-based drug design, informed by cocrystal structures with the protein and small-mol. crystal structures, yielded a series of dihydrobenzofurans. This semisatd. bicycle provided superior druglike properties while maintaining excellent potency and selectivity. Improved physicochem. properties allowed for progression into in vivo experiments, where lead mols. exhibited low clearance and showed target-based inhibition of IRAK4 signaling in an inflammation-mediated PK/PD mouse model.

Journal of Medicinal Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C6H12N2O, Application of Piperidine-4-carboxamide.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Krajewska, Malgorzata published the artcileCDK12 loss in cancer cells affects DNA damage response genes through premature cleavage and polyadenylation, Synthetic Route of 1702809-17-3, the publication is Nature Communications (2019), 10(1), 1-16, database is CAplus and MEDLINE.

Cyclin-dependent kinase 12 (CDK12) modulates transcription elongation by phosphorylating the carboxy-terminal domain of RNA polymerase II and selectively affects the expression of genes involved in the DNA damage response (DDR) and mRNA processing. Yet, the mechanisms underlying such selectivity remain unclear. Here we show that CDK12 inhibition in cancer cells lacking CDK12 mutations results in gene length-dependent elongation defects, inducing premature cleavage and polyadenylation (PCPA) and loss of expression of long (>45 kb) genes, a substantial proportion of which participate in the DDR. This early termination phenotype correlates with an increased number of intronic polyadenylation sites, a feature especially prominent among DDR genes. Phosphoproteomic anal. indicated that CDK12 directly phosphorylates pre-mRNA processing factors, including those regulating PCPA. These results support a model in which DDR genes are uniquely susceptible to CDK12 inhibition primarily due to their relatively longer lengths and lower ratios of U1 snRNP binding to intronic polyadenylation sites.

Nature Communications published new progress about 1702809-17-3. 1702809-17-3 belongs to piperidines, auxiliary class Cell Cycle,CDK, name is (R,E)-N-(4-(3-((5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidine-1-carbonyl)phenyl)-4-(dimethylamino)but-2-enamide, and the molecular formula is C30H32ClN7O2, Synthetic Route of 1702809-17-3.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Vil’yams, V. V. published the artcileRing isomerization of nitrogen heterocycles. Reaction of N-methyl-3-aminomethylpiperidine with nitrous acid, Application In Synthesis of 14613-37-7, the publication is Doklady TSKhA (1965), No. 115(Pt. 1), 247-53, database is CAplus.

N-Methyl-3-aminomethylpiperidine (I) diazotized under the conditions of Demjanov rearrangement gave 39.8% N-methyl-3-hydroxymethylpiperidine (II), about 5% N-methyl-3-methyltetrahydropyridine (III), and 15% 1-methyl-1,5,5,6-tetrahydro-2H-azepine (IV). To the ice-cooled solution of 25.6 g. I and 28.8 g. 85% H₃PO₄ in 200 cc. H₂O was added 14.5 g. NaNO₂ in 50 cc. H₂O, the mixture heated, saturated with Na₂CO₃, and extracted with dichloroethane to give 1.14 g. 1:4.4 mixture of III and IV (b₅₅ 84-90°, d²⁰₂₀0 0.8514, n²⁰_D 1.4585, MR_D 35.61), 10.27 g. of II, b_1.5 63-4°, d²⁰₂₀ 0.9745, n²⁰_D 1.4771, δ₂₀ 34.69 erg/cm.², MR_D 37.47; chloroplatinate m. 213° (decomposition) (EtOH-Et₂O). II was also obtained in 74.9% yield by reduction of ethyl N-methyl nicotinate (V) with LiAlH₄ in Et₂O. V, b₁ 46-7°, d²⁰₂₀ 0.9773, n²⁰_D 1.4545, MR_D 47.175, was prepared in 89.3% yield as follows: 15.1 g. Et nicotinate was refluxed 6 hrs. with 21.3 g. MeI in 50 cc. MeOH, the solvent evaporated, the residue dissolved in 50 cc. H₂O, and the solution treated with freshly prepared AgCl (from 25.5 g. AgNO₃ and 9.36 g. NaCl) and after filtration hydrogenated over Pt at 3 atm. 23 references.

Doklady TSKhA published new progress about 14613-37-7. 14613-37-7 belongs to piperidines, auxiliary class Piperidine,Amine, name is (1-Methylpiperidin-3-yl)methanamine, and the molecular formula is C14H12O2, Application In Synthesis of 14613-37-7.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Vil’yams, V. V. published the artcileThe ring isomerization in some nitrogen-containing heterocyclic compounds. Synthesis of amino and hydroxy derivatives of β-methylpiperidine, Formula: C7H16N2, the publication is Dokl., Rossiisk. Sel’skokhoz. Akad. (1964), 553-7, database is CAplus.

The synthesis of 1-methyl-3-(aminomethyl)piperidine (I) and 3-piperidinylmethanol (II) was described. A mixture of 61 g. nicotinamide, 106.5 g. MeI, 200 ml. MeOH, and a trace of nicotinamide methiodide was refluxed 3 hrs., the solution evaporated in vacuo, the residue dissolved in 150 ml. H₂O and boiled with freshly prepared AgCl (from 120 g. AgNO₃ and 42 g. NaCl) for 5 hrs. The reaction mixture was filtered (charcoal) and hydrogenated over 0.4 g. PtO₂ 36 hrs. at 3.5-1.5 atm. to give 87% nipecotamide methochloride (III), m. 239°. III heated with an equal amount P₂O₅ 5 hrs. at 180°, treated with hot H₂O, neutralized with K₂CO₃, and extracted with AcOEt yielded 76% 1-methyl-3-cyanopiperidine (IV), b₂₃ 106°, b₁₄ 92°, n²⁰_D 1.4630, d²⁰₂₀ 0.9560, surface tension σ₂₀ 34.34 ergs/cm.² To a solution of 6.5 g. LiAlH₄ in 600 ml. absolute Et₂O at 0°, a solution of 25 g. IV in 200 ml. absolute Et₂O was added dropwise during 2 hrs., and the mixture left overnight at room temperature and then refluxed 1.5 hrs. After the usual treatment, 89% I was obtained, b₄ 52°, n²⁰_D 1.4739, d²⁰₂₀ 0.9096, σ₂₀ 32.67 ergs/cm.² [I.PtCl₆ m. 212° (decomposition); I.(AuCl₄)₂ m. 177° (decomposition); picrate m. 234° (decomposition)]. A solution of 30.2 g. Et nicotinate (b₃ 77-80°, n¹⁶_D 1.504, d¹⁶₁₆ 1.1136, σ₂₀ 37.23 ergs/cm.²) in 600 ml. absolute EtOH was added to 62 g. Na, the reaction completed by short refluxing, and the solution decomposed by addition of 150 ml. H₂O, concentrated in vacuo, and extracted with AcOEt. After fractionation, 57% II was obtained, b₃ 103-4°, n²⁰_D 1.4971, d²⁰₂₀ 1.0283, σ₂₀ 44.39 ergs/cm.²

Dokl., Rossiisk. Sel’skokhoz. Akad. published new progress about 14613-37-7. 14613-37-7 belongs to piperidines, auxiliary class Piperidine,Amine, name is (1-Methylpiperidin-3-yl)methanamine, and the molecular formula is C3H6O2, Formula: C7H16N2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem