Day: November 21, 2022

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

Grandberg, I. I. published the artcileDemjanov rearrangement in a series of nitrogenous heterocycles, Application In Synthesis of 14613-37-7, the publication is Doklady TSKhA (1970), 226-31, database is CAplus.

Three isomeric compounds, 2-, 3- and 4-aminomethyl-N-methylpiperidine, were diazotized and the degradation products obtained at 0°, pH 5.5, separated and identified. The 2-substituted derivative gave 2-hydroxymethyl-N-methylpiperidine, 6-methylaminohexan-2-one, 1,2-dimethylpiperidin-2-one, and 2,3-dehydro-1-methylhexamethylenimine in the proportion 49:16:-26:9. The 3-substituted derivative gave 3-hydroxymethyl-N-methylpiperidine, 3(4)-hydroxy-1-methylhexamethylenimine, 1,-3-dimethyl-3-hydroxypiperidine, 2 unsaturated piperidine derivatives (estimated together) and an unsaturated hexamethylenimine derivatives in the proportion 62:2:14:16:6. The ratios of corresponding products with the 4-substituted derivative were 38:1:39:16:6. Two mechanisms based on the conformation of the piperidine ring are proposed to explain the unusually low ratio of rearrangement products and the predominance of H over C atom migration in these reactions.

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 C7H16N2, Application In Synthesis of 14613-37-7.

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

Wang, Xiaolei published the artcileEfficient activation of peroxymonosulfate by copper sulfide for diethyl phthalate degradation: Performance, radical generation and mechanism, HPLC of Formula: 826-36-8, the publication is Science of the Total Environment (2020), 142387, database is CAplus and MEDLINE.

Copper-containing minerals have been extensively used in Fenton-like processes for degradation of pollutants and have exhibited great potential for environmental remediation. This work reports the first use of copper sulfide (CuS), a typical Cu-mineral, for the activation of peroxymonosulfate (PMS) for pollutant degradation; the study also elucidates the underlying mechanism of these processes. Copper sulfide effectively activated PMS to degrade di-Et phthalate (DEP). ESR, free radical quenching, XPS, X-ray diffraction analyses and DFT calculations confirmed that Ξ Cu (I)/ ΞCu (II) cycling on the surface of CuS provided the main pathway to activate PMS to produce highly oxidative species. Unlike conventional sulfate radical-based PMS activation processes, hydroxyl radical (·OH) were found to be the dominant radical in the tested CuS/PMS system, which performed more efficiently than an alternative ·OH-based oxidation system (CuS/H₂O₂) for DEP degradation In addition, the presence of anions such Cl- and NO^-3 has limited inhibition effects on DEP degradation Overall, this study provides an efficient pathway for PMS-based environmental remediation as well as a new insight into the mechanism of PMS activation by Cu-containing minerals.

Science of the Total Environment published new progress about 826-36-8. 826-36-8 belongs to piperidines, auxiliary class Natural product, name is 2,2,6,6-Tetramethylpiperidin-4-one, and the molecular formula is C6H10O7, HPLC of Formula: 826-36-8.

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

Yang, Xianglong published the artcileSuperoxide anion and singlet oxygen dominated faster photocatalytic elimination of nitric oxide over defective bismuth molybdates heterojunctions, Quality Control of 826-36-8, the publication is Journal of Colloid and Interface Science (2022), 248-258, database is CAplus and MEDLINE.

Establishing an ideal photocatalytic system with efficient reactive oxygen species (ROS) generation has been regarded as the linchpin for realizing efficient nitric oxide (NO) removal and unveiling the ROS-mediated mechanism. In this work, a novel oxygen-deficient 0D/1D Bi_3.64Mo_0.36O_6.55/Bi₂MoO₆ heterojunctions (BMO-12-H) were successfully synthesized under the enlightenment of clarified crystal growth mechanism of bismuth molybdates. Because of the synergies between defect-engineering and heterojunction-construction, BMO-12-H demonstrated improved photoelectrochem. properties and O₂ adsorption capacity, which in turn facilitated the ROS generation and conversion. The enhancement of •O_-2 and ¹O₂ endowed BMO-12-H with strengthened NO removal efficiency (59%) with a rate constant of 12.6*10^-2 min^-1. A conceivable NO removal mechanism dominated by •O_-2 and ¹O₂ was proposed and verified based on the theor. calculations and in-situ IR spectroscopy tests, where hazardous NO was oxidized following two different exothermic pathways: the •O_-2-induced NO → NO_-3 process and the ¹O₂-induced NO → NO₂ → NO_-3 process. This work offers a basic guideline for accelerating ROS generation by integrating defect-engineering and heterojunction-construction, and provides new insights into the mechanism of efficient NO removal dominated by •O_-2 and ¹O₂.

Journal of Colloid and Interface Science published new progress about 826-36-8. 826-36-8 belongs to piperidines, auxiliary class Natural product, name is 2,2,6,6-Tetramethylpiperidin-4-one, and the molecular formula is C10H10CoF6P, Quality Control of 826-36-8.

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

Herbrandson, Harry F. published the artcileDerivatives of aromatic sulfinic acids. II. The reaction of thionyl chloride with sulfinic esters, Safety of 1-(Phenylsulfinyl)piperidine, the publication is Journal of the American Chemical Society (1956), 2576-8, database is CAplus.

cf. C.A. 49, 9370i. PhSOCl (22.5 g.) added to 11.1 g. dry pyridine and 5 g. absolute MeOH in 60 cc. dry Et₂O, the mixture kept at -10° until no more precipitate was formed, and diluted with H₂O, the Et₂O layer washed, dried, and evaporated, and the residue distilled yielded 14.0 g. PhSO₂Me (I), b_0.04 67-8°, b_0.03 63°, n_D²⁰ 1.5400. In the same manner was prepared p-MeC₆H₄SO₂Me (II), 91%, b_0.001 68°, n_D²⁰ 1.5380. II (20.1 g.) and 14.0 g. pure SOCl₂ kept a few days in the dark and distilled gave 3.5 g. ClCO₂Me, b. 104-6°, n_D²⁰ 1.4629, and 18.7 g. p-MeC₆H₄SOCl, lemon-yellow oil, b_0.012 79°, n_D²⁰ 1.6007; it gave with NH₃ in dry Et₂O the p-MeC₆H₄SONH₂, m. 120-20.5° (from aqueous EtOH). I gave in the same manner 84% PhSOCl, yellow oil, b_0.012 65° [PhSONH₂, m. 122° (from aqueous EtOH); piperidide, m. 82-3° (from petr. ether)]. l-Menthyl 1-p-toluenesulfinate (III), m. 106-7° (corrected), [α]_D²⁵ -199.19° (c 2, Me₂CO), was prepared by the method of Phillips (C.A. 20, 397). Et₄NBr in H₂O treated with a slight excess Ag₂O, the mixture triturated twice, and the filtrate acidified to Congo red with 20% HCl and evaporated gave Et₄NCl (IV). A series of kinetic runs was carried out with III and SOCl₂ in PhNO₂ at 24.88 ± 0.05° (molar concentrations of IV, SOCl₂, and IV, and k × 10⁴ sec.^-1 given): 0.0554, 0.0616, 0.00093, 0.62; 0.0551, 0.0616, 0.00-213, 1.18; 0.0626, 0.0616, 0.00309, 1.68; 0.0590, 0.123, 0.00309, 1.92; 0.0516, 0.0616, 0.00425, 2.30; 0.0604, 0.0616, 0.00463, 2.06; 0.0779, 0.0616, 0.00463, 2.12; 0.0520, 0.0616, 0.00850, 3.55; 0.0409, 0.0616, 0.0106, 3.80; 0.0635, 0.0616, 0.0160, 4.28; 0.0548, 0.0492, 0.0213, 3.82; 0.0423, 0.0492, 0.0213, 4.24; 0.0774, 0.123, 0, 0; 0.0542, 0, 0.00617, 0; 0.0845, 0, 0.0213,0; 0.0663, 0, – (0.00525 HCl), 0; 0.0594, 0.0616, – (0.00525 HCl), 0; 0.0510, 0.0616, 0.00378 (MeOH), 0; 0.0408, 0.0616, – (0.0035 H₂O), 0; 0.0732, 0.0860, 0.0232, 7.30; 0.0703, 0.0860, 0.0232 + 0.1M SO₂, 7.63. In the absence of added chloride the reaction is slow; it is 1st order in ester and 1st order in added chloride ion. Trace impurities of the SOCl₂, probably mainly HCl, also affect the rate.

Journal of the American Chemical Society published new progress about 4972-31-0. 4972-31-0 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-(Phenylsulfinyl)piperidine, and the molecular formula is C11H15NOS, Safety of 1-(Phenylsulfinyl)piperidine.

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

Mohd Sarofil, Anith Dzhanxinah published the artcileToad egg-like bismuth nanoparticles encapsulated in an N-doped carbon microrod via supercritical acetone as anodes in lithium-ion batteries, Computed Properties of 826-36-8, the publication is Journal of Industrial and Engineering Chemistry (Amsterdam, Netherlands) (2022), 128-141, database is CAplus.

A toad egg-inspired structure comprising bismuth (Bi) nanoparticles (NPs) contained in a carbon microrod shell (Bi@C) was synthesized via the one-pot supercritical acetone (scAct) route and subsequent carbonization. During the formation of Bi NPs in scAct in the presence of nitric acid, a few decomposed acetone mols. acted as carbon sources, which generated an albumen-like N-doped carbon microrod with an average shell thickness of 38 nm and were embedded with yolk-like Bi NPs having size in the range of 30-200 nm. The densely packed Bi NPs inside the carbon micron shell resulted in a high Bi loading of 78 wt%. When utilized for Li storage, the Bi@C delivered a high reversible capacity of 337 mAh g^-1 after 70 cycles at 0.05 A g^-1, long-term cyclability of 0.04 decay per cycle for 1000 cycles at 1 A g^-1, and high volumetric energy d. of 870 mAh cm^-3. The use of a mixed ether- and ester-based electrolyte in the Bi@C cell reduced the resistivity and increased the capacitive contribution, thereby resulting in a better high-rate performance and long-term stability than those obtained using conventional ester-based electrolytes.

Journal of Industrial and Engineering Chemistry (Amsterdam, Netherlands) published new progress about 826-36-8. 826-36-8 belongs to piperidines, auxiliary class Natural product, name is 2,2,6,6-Tetramethylpiperidin-4-one, and the molecular formula is C9H17NO, Computed Properties of 826-36-8.

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