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Methyl carbamate

Methyl carbamate is a chemical compound with the formula CH3OCONH2.
It is a white crystalline solid that is soluble in water and organic solvents.
Methyl carbamate is used as an insecticide, fungicide, and herbicide, as well as in the production of other chemicals.
Exposure to methyl carbamate can result in cholinergic effects, such as nausea, vomiting, diarrhea, and breathing difficulties.
Proper precautions should be taken when handling this substance.
Reasearchers studying methyl carbamate can utilize PubCompare.ai's AI-powered protocol comparison tools to locate relevant publications, preprints, and patents, and identify the most reproducible and accurate methods for their work.

Most cited protocols related to «Methyl carbamate»

Cytotoxicity Assay with DNA-Damaging Agents

Cited 6 times

HeLa cells stably expressing hABH2_1–10-YFP and YFP were seeded into 96-well plates (4,000 cells/well) and incubated for 3 h. Various doses of MMS (Acros Organics), BCNU (1,3-Bis(2-chloroethyl)-1-nitrosurea; Sigma-Aldrich), TMZ (4-methyl-5-oxo-2,3,4,6,8-pentazabicyclo [4.3.0] nona-2,7,9-triene-9-carboxamide; Sigma-Aldrich), and MMC (6-amino-1,1a,2,8,8a,8b-hexahydro-8-(hydroxymethyl)-8a-methoxy-5-methyl-azirino[2’,3′:3,4] pyrrolo[1,2-a]indole-4,7-dione carbamate; Sigma-Aldrich) were added to the wells. The cells were exposed continuously until harvest. MTT was added to the cells, the OD was measured at 570 nm, the mean from at least six wells was used to calculate cell survival, and the SD was smaller than the size of the dots. Data presented show growth from one representative experiment and has been reproduced at least two times.

Gilljam K.M., Feyzi E., Aas P.A., Sousa M.M., Müller R., Vågbø C.B., Catterall T.C., Liabakk N.B., Slupphaug G., Drabløs F., Krokan H.E, & Otterlei M. (2009). Identification of a novel, widespread, and functionally important PCNA-binding motif. The Journal of Cell Biology, 186(5), 645-654.

Publication 2009

Carbamates Carmustine Cells Cell Survival HeLa Cells indole Nitrosourea Compounds

Synthesis and Characterization of Sugar Derivatives

Cited 6 times

NMR spectra were recorded with an Agilent spectrometer at a frequency of 400 MHz using TMS or DSS as the internal standards and CDCl₃, CD₃OD, DMSO-d6 or D₂O as the solvents. NMR solvents were purchased from ACROS Organics (Geel, Belgium). Chemical shifts (δ) are expressed in ppm and coupling constants (J) in Hz. The following abbreviations were used to explain the observed multiplicities: s: singlet, d: doublet, dd: doublet of doublets, ddd: doublet of doublet of doublets, t: triplet, dd-t: doublet of doublets resembling a triplet (with similar values of coupling constants), m: multiplet, p: pentet (quintet), b: broad. High-resolution mass spectra (HRMS) were recorded with a WATERS LCT Premier XE system using the electrospray-ionization (ESI) technique. Optical rotations were measured with a JASCO P-2000 polarimeter using a sodium lamp (589.3 nm) at room temperature. Melting point measurements were performed on OptiMelt (MPA 100) Stanford Research Systems. Reactions were monitored by thin-layer chromatography (TLC) on precoated plates of silica gel 60 F254 (Merck Millipore, Burlington, MA, USA). The TLC plates were visualized under UV light (λ = 254 nm) or by charring the plates after spraying with 10% solution of sulfuric acid in ethanol. Crude products were purified using column chromatography performed on Silica Gel 60 (70–230 mesh, Fluka, St. Louis, MI, USA), developed using toluene:EtOAc or CHCl₃:MeOH as solvent systems. All evaporations were performed on a rotary evaporator under diminished pressure at 40 °C. Reversed-phase HPLC analyses were performed using JASCO LC 2000 apparatus equipped with a reverse-phase column (Nucleosil 100 C18.5 μm, 25 × 0.4 cm; mobile phase: H₂O/MeCN 90:10, flow rate 0.8 mL/min) with a fluorescence detector (FP). Fluorescence for substrate and product was read at 385 nm excitation/540 nm emission. The absorbance on MTT assay was measured spectrophotometrically at the 570 nm wavelength using a plate reader (Epoch, BioTek, USA).
All of the chemicals used in the experiments were purchased from Sigma-Aldrich, ACROS Organics, Fluka and Avantor and were used without purification. 8-Hydroxyquinoline 1, 8-hydroxyquinaldine 2, D-glucose 11 and D-galactose 12 are commercially available (Sigma-Aldrich). 8-(2-Propyn-1-yloxy)quinoline 3 [57 (link)], 2-methyl-8-(2-propyn-1-yloxy)quinoline 4 [57 (link)], 1,2,3,4,6-penta-O-acetyl-β-D-glucopyranose 13 [54 (link)], 1,2,3,4,6-penta-O-acetyl-β-D-galactopyranose 14 [54 (link)], 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide 15 [54 (link)], 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide 16 [54 (link)], 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl azide 17 [54 (link)], 2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl azide 18 [54 (link)], 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl amine 19 [60 (link)], 2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl amine 20 [60 (link)], propargyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside 21 [61 (link)], propargyl 2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside 22 [61 (link)], 2-bromoethyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside 25 [62 (link)], 2-bromoethyl 2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside 26 [62 (link)], 2-azidoethyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside 27 [62 (link)], 2-azidoethyl 2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside 28 [62 (link)], 2,3,4,6-tetra-O-acetyl-N-(β-D-glucopyranosyl)propiolamide 37 [65 (link)], 2,3,4,6-tetra-O-acetyl-N-(β-D-galactopyranosyl)propiolamide 38 [65 (link)], 2,3,4,6-tetra-O-acetyl-N-(β-D-glucopyranosyl)-O-propargyl carbamate 41 [66 (link)] and 2,3,4,6-tetra-O-acetyl-N-(β-D-galactopyranosyl)-O-propargyl carbamate 42 [66 (link)] were prepared according to the respective published procedures. Propargyl β-D-glucopyranoside 23, propargyl β-D-galactopyranoside 24, 2-azidoethyl β-D-glucopyranoside 29, 2-azidoethyl β-D-galactopyranoside 30, N-(β-D-glucopyranosyl)azidoacetamide 35, N-(β-D-galactopyranosyl)azidoacetamide 36, N-(β-D-glucopyranosyl)propiolamide 39, N-(β-D-galactopyranosyl)propiolamide 40N-(β-D-glucopyranosyl)-O-propargyl carbamate 43, N-(β-D-galactopyranosyl)-O-propargyl carbamate 44 were obtained by Zemplén protocol [67 (link)] by deacetylation of the corresponding sugar derivatives.

Krawczyk M., Pastuch-Gawołek G., Pluta A., Erfurt K., Domiński A, & Kurcok P. (2019). 8-Hydroxyquinoline Glycoconjugates: Modifications in the Linker Structure and Their Effect on the Cytotoxicity of the Obtained Compounds. Molecules, 24(22), 4181.

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Publication 2019

Genetic engineering of fission yeast

Cited 5 times

S. pombe strains used in this study are listed in Table 1. PCR-based gene targeting was performed as described [90] (link). All tagged genes are under the control of endogenous promoters and integrated at their native chromosomal loci except those under the control of 3nmt1 and 41nmt1 promoters.
To construct the pom1-pom2K strain for the domain complementation experiments, the Pom1 kinase domain (amino acids 699–995) was replaced by KS-ura4 using PCR-based gene targeting to obtain strain pom1-ΔK::ura4⁺[90] (link). DNA (pom2K) encoding the Pom2 kinase domain (amino acids 518–814) was amplified and cloned into the TOPO vector. PCR fidelity was confirmed by sequencing. Then the ura4⁺ in pom1-ΔK::ura4⁺ was replaced by the pom2K fragment with 66 bp-long homologous sequences to the flanking regions of pom1 kinase domain. Positive clones were selected on 5-FOA plates and confirmed by PCR. The fusion gene was further confirmed by sequencing.
Cells were re-streaked from −80°C stock, grown 2–3 days on plates, and then inoculated into 5–15 ml YE5S liquid culture as described [91] (link). Cultures were kept in exponential phase for 36–48 h before microscopy except where specified. Strains with 3nmt1 or 41nmt1 promoter were grown in YE5S medium for at least 24 h, washed 3× with EMM5S, and then induced in EMM5S medium for 12–48 h before microscopy except where noted. Stock solutions of thiabendazole (TBZ; Sigma-Aldrich) and methyl benzimidazole-2-yl carbamate (MBC; Sigma-Aldrich) were made in DMSO at concentrations of 50 mg/ml and 5 mg/ml, respectively. The final working concentrations were 50 µg/ml for TBZ and 25 µg/ml for MBC. Cells were stained with Calcofluor and Hoechst 33342 (bisBenzimide) as described [92] (link). Stock solution of Hoechst 33342 (Sigma-Aldrich) was made in ddH₂O at 1 mg/ml and kept in the dark at 4°C.

Wu P., Zhao R., Ye Y, & Wu J.Q. (2011). Roles of the DYRK Kinase Pom2 in Cytokinesis, Mitochondrial Morphology, and Sporulation in Fission Yeast. PLoS ONE, 6(12), e28000.

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Publication 2011

Amino Acids benzimidazole Bisbenzimidazole Trihydrochloride Cells Chromosomes Clone Cells Cloning Vectors Genes Genes, Reporter HOE 33342 Homologous Sequences methyl carbamate Microscopy Phosphotransferases Schizosaccharomyces pombe Strains Sulfoxide, Dimethyl Topotecan

Prenatal Pesticide Exposure Assessment

Cited 4 times

We geocoded maternal residential addresses listed on the birth certificates using an automated approach [32 (link)] and calculated measures of residential ambient pesticide exposure using a GIS-based Residential Ambient Pesticide Estimation System, as previously described [33 (link),34 (link)]. In brief, we combined California’s Pesticide Use Reports (PUR), land use maps, and geocoded birth addresses to produce estimates of pesticide exposure during each month of pregnancy (see Supplementary Materials and Methods in Appendix A). Monthly exposure estimates (pounds per acre) were calculated by adding the poundage of pesticide applied in a 2 km buffer surrounding each address and weighting the total poundage by the proportion of acreage treated within the buffer. We defined the first, second, and third trimesters as 0–12 weeks, 13–25 weeks, and ≥26 weeks of pregnancy, respectively. For preterm births, the length of gestation and hence, the exposure period are shorter than those of term birth by design; to account for this, we assessed third trimester exposure at 27–32 weeks of gestation only (>88% of preterm births had a gestational length longer than 32 weeks). For each pesticide, monthly values were divided into the daily poundage for each gestational day of pregnancy which was then averaged across all days in each trimester. Due to the uncertainty in this type of exposure assessment (e.g., assuming the mothers stayed at the reported residences during the entire pregnancy, wind patterns), we categorized prenatal exposure as ever/never exposed to a specific chemical in each trimester.
We selected 17 individual chemicals previously observed to have reproductive toxicity [24 (link),35 (link),36 (link),37 (link),38 (link),39 (link)]. Additionally, we considered all pesticides from three widely used chemical classes in the Pesticide Action Network (PAN) pesticide database (http://www.pesticideinfo.org/) that have been linked to reproductive toxicity [21 (link),37 (link),40 (link),41 (link)], i.e., 24 N-methyl carbamate/dithiocarbamates, 50 organophosphates, and 29 pyrethroid pesticides, to which one or more study subjects were exposed according to our 2 km buffer criterion (Table S1). Briefly, for each trimester, we identified whether mothers were ever or never exposed (1 vs. 0) to selected individual chemicals within each chemical class; for each chemical class, we generated a count which we categorized into three levels (exposed to 2 or more pesticides, exposed to 1 pesticide, and no exposure).
Since the specific locations of non-agricultural pesticide applications (structural pest control, rights of way, and landscape maintenance in urban communities) are not provided by the PUR, and due to competing exposures such as air pollution in urban areas [42 (link),43 (link)], we restricted our analyses to individuals born in agricultural regions, defined as residences within a 2 km buffer of any type of agricultural pesticide application during pregnancy (Figure S1).

Ling C., Liew Z., von Ehrenstein O.S., Heck J.E., Park A.S., Cui X., Cockburn M., Wu J, & Ritz B. (2018). Prenatal Exposure to Ambient Pesticides and Preterm Birth and Term Low Birthweight in Agricultural Regions of California. Toxics, 6(3), 41.

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Publication 2018

Air Pollution Birth Buffers Chemical Actions Childbirth Flatulence methyl carbamate Microtubule-Associated Proteins Mothers Organophosphates Pesticides Pregnancy Premature Birth Pyrethroids Reproduction Residency Term Birth

Synthesis of Azole-Substituted Propanamides

Cited 4 times

All reagents and solvents were of general purpose or analytical grade and purchased from Sigma‐Aldrich, Fisher Scientific, Fluka, Alfa Aesar and Acros. Lanosterol and fluconazole were supplied by Sigma‐Aldrich. Ni²⁺‐NTA agarose affinity chromatography matrix was obtained from Qiagen. ¹H and ¹³C NMR spectra were recorded with a Bruker Avance DPX500 spectrometer operating at 500 and 125 MHz, with Me₄Si as internal standard. Mass spectra (HRMS) were determined by the Engineering and Physical Sciences Research Council National Mass Spectrometry Service Centre at Swansea University (Swansea, UK). Elemental analysis was performed by MEDAC Ltd (Chobham, Surrey, UK); HPLC (Method A, Cardiff University) was performed on a Shimadzu LC‐2030C Plus C18 Rapid Resolution 250×4.6 mm, 5 μm particle size using a 7–10 min gradient of water/methanol 5 : 95 (Method B, University of Bath) was performed on a Zorbax Eclipse Plus C18 Rapid Resolution 2.1×50 mm, 1.8 μm particle size using a 7.5 minute gradient method 5 : 95 water: methanol with 0.1 % formic acid as additive. Gradient column chromatography was performed with silica gel 60 (230‐400 mesh; Merck) and TLC was carried out on precoated silica plates (kiesel gel 60 F₂₅₄, BDH). Compounds were visualised by illumination under UV light (254 nm) or by the use of vanillin stain followed by heating. Melting points were determined on an electrothermal instrument and are uncorrected. All solvents were dried prior to use and stored over 4 Å molecular sieves, under nitrogen. All the compounds were≥95 % pure.
General procedure for the preparation of azoles (5 and 12) and alkene elimination products (6 and 13). To a stirred solution of azole (imidazole or triazole or tetrazole; 4 equiv) in dry CH₃CN (2 mL/mmol of azole) was added potassium carbonate (4 equiv), and the mixture was heated for 1 h at 45 °C. After cooling to room temperature, mesylate (4 or 11; 1 equiv) was added and the reaction was heated at 70 °C for 4 h then stirred at room temperature overnight. The solvent was evaporated under vacuum and the residue was extracted with EtOAc (35 mL/mmol of mesylate), washed with brine (3×35 mL/mmol of mesylate) and water (3×35 mL/mmol of mesylate). The organic layer was dried (MgSO₄) and evaporated under vacuum to give the crude product, which was purified by gradient column chromatography. Alkene (6 or 13) was eluted first with petroleum ether/EtOAc system, followed by the azole product (5 or 12) on changing the system to CH₂Cl₂/MeOH.
N‐Benzyl‐2‐phenylacrylamide (6 a, R¹=R²=H). Prepared from 3‐(benzylamino)‐3‐oxo‐2‐phenylpropyl methanesulfonate (4 a; 0.48 g, 1.44 mmol) and purified by petroleum ether/EtOAc gradient column chromatography eluting with 70 : 30 v/v. Product was obtained as a white solid, yield 0.27 g (62 %); m.p. 78–80 °C; TLC (petroleum ether/EtOAc 1 : 1, v/v), R_f=0.78; ¹H NMR ([D₆]DMSO): δ 8.74 (t, J=5.9 Hz, 1H, NH), 7.43 (m, 2H, Ar), 7.35 (m, 7H, Ar), 7.26 (m, 1H, Ar), 5.79 (s, 1H, C=CHaHb), 5.68 (s, 1H, C=CHaHb), 4.40 (d, J=6.1 Hz, 2H, NHCH₂); ¹³C NMR ([D₆]DMSO): δ 168.70 (C, C=O), 145.65 (C, C=CH₂), 140.07 (C, Ar), 137.18 (C, Ar), 128.79 (2×CH, Ar), 128.77 (2×CH, Ar), 128.57 (CH, Ar), 127.61 (2×CH, Ar), 127.52 (2×CH, Ar), 127.21 (CH, Ar), 118.17 (C=CH₂), 42.81 (NHCH₂); HRMS (ESI), m/z calcd for C₁₆H₁₆NO ([M+H]⁺), 238.1257; found: 238.1226.
N‐(4‐Fluorobenzyl)‐3‐(1H‐imidazol‐1‐yl)‐2‐phenylpropanamide (5 b, R¹=4‐F, R²=H) andN‐(4‐fluorobenzyl)‐2‐phenylacrylamide (6 b, R¹=4‐F, R²=H). Prepared from 3‐((4‐fluorobenzyl)amino)‐3‐oxo‐2‐phenylpropyl methanesulfonate (4 b; 0.70 g, 1.98 mmol) and purified by gradient column chromatography eluting the alkene (6 b) with petroleum ether/EtOAc 70 : 30 v/v, followed by the imidazole (5 b) with CH₂Cl₂/MeOH 90 : 10 v/v. N‐(4‐Fluorobenzyl)‐3‐(1H‐imidazol‐1‐yl)‐2‐phenylpropanamide (5 b) was obtained as a cream solid, yield 0.22 g (34 %); m.p. 100–102 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.0; ¹H NMR ([D₆]DMSO): δ 8.61 (t, J=5.9 Hz, 1H, NH), 7.53 (brs, 1H, imid), 7.40 (d, J=7.05 Hz, 2H, Ar), 7.34 (t, J=7.4 Hz, 2H, Ar), 7.29 (t, J=7.2 Hz, 1H, Ar), 7.11 (brs, 1H, imid), 7.03 (m, 4H, Ar), 6.88 (brs, 1H, imid), 4.63 (dd, J=9.7, 13.4 Hz, 1H, CHCHaHb), 4.29 (dd, J=6.4, 15.3 Hz, 1H, NHCHaHb), 4.24 (dd, J=5.7, 13.4 Hz, CHCHaHb), 4.10 (dd, J=5.5, 15.2 Hz, NHCHaHb), 4.02 (dd, J=5.8, 9.6 Hz, CHCHaHb); ¹³C NMR ([D₆]DMSO): δ 171.06 (C, C=O), 162.52 and 160.60 (C,C−F), 137.94 (C, Ar), 135.63 (C, Ar), 130.15 (CH, imid), 130.09 (CH, imid), 129.38 (CH, Ar), 129.32 (CH, Ar), 128.93 (2×CH, Ar), 128.27 (2×CH, Ar), 127.86 (CH, Ar), 115.66 (CH, imid), 115.40 (CH, Ar), 115.23 (CH, Ar), 53.33 (CHCH₂imid), 48.88 (CHCH₂imid), 41.80 (NHCH₂); LRMS (ES, m/z): 324.15 [C₁₉H₁₈FN₃O+H]⁺; HRMS (ESI), m/z calcd for C₁₉H₁₉FN₃O ([M+H]⁺), 324.1507; found: 324.1507; HPLC (Method A): 98.0 %, t_R=4.87 min. N‐(4‐Fluorobenzyl)‐2‐phenylacrylamide (6 b) was obtained as a white solid, yield 0.25 g (39 %); m.p. 108–110 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.79; ¹H NMR ([D₆]DMSO): δ 8.74 (t, J=5.4 Hz, 1H, NH), 7.43 (d, J=7.7 Hz, 2H, Ar), 7.36 (m, 5H, Ar), 7.17 (t, J=8.9 Hz, 2H, Ar), 5.79 (s, 1H, C=CHaHb), 5.69 (s, 1H, C=CHaHb), 4.38 (d, J=6.0 Hz, 2H, NHCH₂); ¹³C NMR ([D₆]DMSO): δ 168.68 (C, C=O), 162.60 and 160.67 (C, C−F), 145.60 (C, Ar), 137.16 (C, Ar), 136.27 (C, C=CH₂), 129.67 (CH, Ar), 129.61 (CH, Ar), 128.79 (2×CH, Ar), 128.58 (CH, Ar), 127.53 (2×CH, Ar), 118.29 (C=CH₂), 115.57 (CH, Ar), 115.40 (CH, Ar), 42.16 (NHCH₂); elemental analysis calcd (%) for C₁₆H₁₄FNO (255.2911): C 75.28, H 5.53, N 5.48; found: C 75.34, H 5.32, N 5.55.
N‐(4‐Chlorobenzyl)‐3‐(1H‐imidazol‐1‐yl)‐2‐phenylpropanamide (5 c, R¹=4‐Cl, R²=H). Prepared from 3‐((4‐chlorobenzyl)amino)‐3‐oxo‐2‐phenylpropyl methanesulfonate (4 c; 0.38 g, 1.0 mmol) and purified by gradient column chromatography eluting the imidazole (5 c) with CH₂Cl₂/MeOH 90 : 10 v/v. Product was obtained as a cream solid, yield 0.20 g (56 %); m.p. 136–138 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v), R_f=0.0; ¹H NMR ([D₆]DMSO): δ 8.67 (t, J=5.8 Hz, 1H, NH), 7.52 (s, 1H, imid), 7.40 (m, 2H, Ar), 7.35 (m, 2H, Ar), 7.29 (m, 3H, Ar), 7.11 (s, 1H, imid), 6.96 (d, J=8.2 Hz, 2H, Ar), 6.88 (s, 1H, imid), 4.63 (dd, J=9.9, 13.3 Hz, 1H, CHCHaHb), 4.30 (dd, J=6.4, 15.5 Hz, 1H, NHCHaHb), 4.23 (dd, J=5.6, 13.4 Hz, CHCHaHb), 4.10 (dd, J=5.4, 15.5 Hz, NHCHaHb), 4.03 (dd, J=5.7, 9.7 Hz, CHCHaHb); ¹³C NMR ([D₆]DMSO): δ 171.2 (C, C=O), 138.5 (C, Ar), 137.9 (C, Ar), 131.7 (C, C−Cl), 129.2 (3×CH, Ar (2) and imid (1)), 129.0 (2×CH, Ar), 128.6 (3×CH, Ar (2) and imid (1)), 128.3 (2×CH, Ar), 127.9 (CH, Ar), 120.0 (CH, imid), 53.3 (CHCH₂imid), 50.8 (CHCH₂imid), 41.8 (NHCH₂); elemental analysis calcd (%) for C₁₉H₁₈ClN₃O⋅0.1H₂O (341.6215): C 66.80, H 5.37, N 12.30; found: C 66.44, H 5.07, N 12.39; HPLC (Method A): 99.0 %, t_R=4.94 min.
N‐(4‐Chlorobenzyl)‐2‐(4‐chlorophenyl)‐3(1H‐imidazol‐1‐yl)propanamide (5 d, R¹=R²=4‐Cl) andN‐(4‐chlorobenzyl)‐2‐(4‐chlorophenyl)acrylamide (6 d, R¹=R²=4‐Cl). Prepared from 3‐((4‐chlorobenzyl)amino)‐2‐(4‐chlorophenyl)‐3‐oxopropyl methanesulfonate (4 d; 0.44 g, 1.09 mmol) and purified by gradient column chromatography eluting the alkene (6 d) with petroleum ether/EtOAc 70 : 30 v/v, followed by the imidazole (5 d) with CH₂Cl₂/MeOH 90 : 10 v/v. Imidazole 5 d was further purified by recrystallization from CH₃CN. N‐(4‐Chlorobenzyl)‐2‐(4‐chlorophenyl)‐3(1H‐imidazol‐1‐yl)propanamide (5 d) was obtained as a brown solid, yield 0.11 g (26 %); m.p. 160–162 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.0; ¹H NMR ([D₆]DMSO): δ 8.66 (t, J=5.9 Hz, 1H, NH), 7.50 (s, 1H, imid.), 7.40 (m, 4H, Ar), 7.29 (d, J=8.5 Hz, 2H, Ar), 7.09 (s, 1H, imid.), 6.98 (d, J=8.5 Hz, 2H, Ar), 6.86 (s, 1H, imid.), 4.59 (dd, J=9.4, 13.5 Hz, 1H, CHCHaHb), 4.29 (dd, J=6.4, 15.4 Hz, 1H, NHCHaHb), 4.24 (dd, J=6.1, 13.5 Hz, 1H, CHCHaHb), 4.10 (dd, J=5.4, 15.5 Hz, 1H, NHCHaHb), 4.05 (dd, J=6.1, 9.4 Hz, 1H, CHCHaHb); ¹³C NMR ([D₆]DMSO): δ 170.78 (C, C=O), 138.41 (C, Ar), 138.06 (CH, imid), 136.78 (C, Ar), 132.59 (C, C−Cl), 131.75 (C, C−Cl), 130.16 (2×CH, Ar), 129.23 (2×CH, Ar), 128.92 (2×CH, Ar), 128.68 (CH, imid), 128.57 (2×CH, Ar), 119.95 (CH, imid), 52.59 (CHCH_2‐imid), 48.66 (CHCH₂imid), 41.85 (NHCH₂); elemental analysis calcd (%) for C₁₉H₁₇Cl₂N₃O (374.2688): C 60.97, H 4.58, N 11.22; found: C 60.99, H 4.50, N 11.20; HPLC (Method A): 96.3 %, t_R=2.53 min. N‐(4‐Chlorobenzyl)‐2‐(4‐chlorophenyl)acrylamide (6 d) was obtained as an off‐white solid, yield 0.09 g (22 %); m.p. 108–110 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.73; ¹H NMR ([D₆]DMSO): δ 8.80 (t, J=5.9 Hz, 1H, NH), 7.45 (m, 4H, Ar), 7.41 (d, J=8.5 Hz, 2H, Ar), 7.33 (d, J=8.5 Hz, 2H, Ar), 5.84 (s, 1H, C=CHaHb), 5.76 (s, 1H, C=CHaHb), 4.37 (d, J=6.1 Hz, 2H, NHCH₂); ¹³C NMR ([D₆]DMSO): δ 168.27 (C, C=O), 144.20 (C, C=CH₂), 139.02 (C, Ar), 135.98 (C, C−Cl), 133.27 (C, C−Cl), 131.80 (C, Ar), 129.55 (2×CH, Ar), 129.46 (2×CH, Ar), 128.80 (2×CH, Ar), 128.74 (2×CH, Ar), 119.40 (C=CH₂), 42.26 (NHCH₂); elemental analysis calcd (%) for C₁₆H₁₃Cl₂NO (306.1908): C 62.76, H 4.28, N 4.57; found: C 63.07, H 4.30, N 4.61.
N‐(2,4‐Dichlorobenzyl)‐3‐(1H‐imidazol‐1‐yl)‐2‐phenylpropanamide (5 e, R¹=2,4‐Cl, R²=H) andN‐(2,4‐dichlorobenzyl)‐2‐phenylacrylamide (6 e, R¹=2,4‐Cl, R²=H). Prepared from 3‐((2,4‐dichlorobenzyl)amino)‐3‐oxo‐2‐phenylpropyl methanesulfonate (4 e; 0.5 g, 1.24 mmol) and purified by gradient column chromatography eluting the alkene (6 e) with petroleum ether/EtOAc 80 : 20 v/v, followed by the imidazole (5 e) with CH₂Cl₂/MeOH 90 : 10 v/v. N‐(2,4‐Dichlorobenzyl)‐3‐(1H‐imidazol‐1‐yl)‐2‐phenylpropanamide (5 e) was obtained as a cream solid, yield 0.34 g (74 %); m.p. 55–57 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.0; ¹H NMR ([D₆]DMSO): δ 8.68 (t, J=5.8 Hz, 1H, NH), 7.56 (d, J=2.1 Hz, 1H, Ar), 7.54 (brs, 1H, imid), 7.41 (d, J=7.2 Hz, 2H, Ar), 7.36 (t, J=7.4 Hz, 2H, Ar), 7.30 (t, J=7.2 Hz, 1H, Ar), 7.23 (dd, J=2.1, 8.4 Hz, 1H, Ar), 7.13 (brs, 1H, imid), 6.90 (brs, 1H, imid), 6.75 (d, J=8.4 Hz, 1H, Ar), 4.63 (dd, J=9.8, 13.4 Hz, 1H, CHCHaHb), 4.31 (dd, J=6.2, 16.0 Hz, 1H, NHCHaHb), 4.23 (dd, J=5.7, 13.4 Hz, 1H, CHCHaHb), 4.16 (dd, J=5.4, 16.0 Hz, 1H, NHCHaHb), 4.10 (dd, J=5.7, 9.8 Hz, 1H, CHCHaHb)); ¹³C NMR ([D₆]DMSO): δ 171.32 (C, C=O), 137.72 (C, Ar), 135.52 (C, Ar), 133.34 (C, C−Cl), 132.63 (C, C−Cl), 130.12 (2×CH, Ar (1) and imid (1)), 128.97 (3×CH, Ar), 128.30 (2×CH, Ar), 127.94 (2×CH, Ar (1) and imid (1)), 127.51 (2×CH, Ar (1) and imid (1)), 53.21 (CHCH₂imid), 48.86 (CHCH₂imid), 40.01 (NHCH₂); elemental analysis calcd (%) for C₁₉H₁₇Cl₂N₃O⋅0.2 H₂O (377.87184): C 60.39, H 4.64, N 11.12; found: C 60.04, H 4.46, N 10.85; HPLC (Method A): 96.20 %, t_R=3.20 min. N‐(2,4‐Dichlorobenzyl)‐2‐phenylacrylamide (6 e) was obtained as a cream solid, yield 0.05 g (11 %); m.p. 66–68 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v), R_f=0.85; ¹H NMR ([D₆]DMSO): δ 8.76 (t, J=5.8 Hz, 1H, NH), 7.63 (d, J=2.1 Hz, 1H, Ar), 7.47 (m, 3H, Ar), 7.34 (m, 5H, Ar), 5.83 (s, 1H, C=CHaHb), 5.75 (s, 1H, C=CHaHb), 4.44 (d, J=5.9 Hz, 2H, NHCH₂); ¹³C NMR ([D₆]DMSO): δ 168.87 (C, C=O), 145.33 (C, C=CH₂), 137.04 (C, Ar), 136.02 (C, C−Cl), 133.41 (C, C−Cl), 132.67 (C, Ar), 130.58 (CH, Ar), 129.06 (CH, Ar), 128.82 (2×CH, Ar), 128.63 (CH, Ar), 127.85 (CH, Ar), 127.58 (2×CH, Ar), 118.73 (C=CH₂), 40.01 (NHCH₂); LRMS (ESI, m/z): 308.0417 [C₁₆H₁₃³⁷Cl₂NO+H]⁺, 306.0447 [C₁₆H₁₃³⁵Cl₂NO+H]⁺, 158.98 [C₇H₅³⁵Cl₂]⁺; HRMS (ES), m/z calcd for C₁₆H₁₄³⁵Cl₂NO ([M+H]⁺), 306.0447; found: 306.0449; and calcd for C₁₆H₁₄³⁷Cl₂NO ([M+H]⁺), 308.0417; found: 308.0418.
2‐(4‐Chlorophenyl)‐N‐(2,4‐dichlorobenzyl)‐3‐(1H‐imidazol‐1‐yl)propanamide (5 f, R¹=2,4‐diCl, R²=Cl) and 2‐(4‐chlorophenyl)‐N‐(2,4‐dichlorobenzyl)acrylamide (6 f, R¹=2,4‐diCl, R²=Cl). Prepared from 2‐(4‐chlorophenyl)‐3‐((2,4‐dichlorobenzyl)amino)‐3‐oxopropyl methanesulfonate (4 f; 0.54 g, 1.24 mmoL) and purified by gradient column chromatography eluting the alkene (6 e) with petroleum ether/EtOAc 60 : 40 v/v, followed by the imidazole (5 e) with CH₂Cl₂/MeOH 90 : 10 v/v. 2‐(4‐Chlorophenyl)‐N‐(2,4‐dichlorobenzyl)‐3‐(1H‐imidazol‐1‐yl)propanamide (5 f) was obtained as a white solid, yield 0.21 g (41 %); m.p. 148–150 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.0; ¹H NMR ([D₆]DMSO): δ 8.69 (t, J=5.7 Hz, 1H, NH), 7.56 (d, J=2.2 Hz, 1H, Ar), 7.50 (brs, 1H, imid), 7.41 (m, 4H, Ar), 7.26 (dd, J=2.1, 8.3 Hz, 1H, Ar), 7.10 (brs, 1H, imid), 6.88 (brs, 1H, imid), 6.79 (d, J=8.4 Hz, 1H, Ar), 4.58 (dd, J=9.5, 13.4 Hz, 1H, CHCHaHb), 4.30 (dd, J=6.1, 15.9 Hz, 1H, NHCHaHb), 4.23 (dd, J=6.0, 13.5 Hz, 1H, CHCHaHb), 4.16 (dd, J=5.5, 15.9 Hz, 1H, NHCHaHb), 4.10 (dd, J=6.0, 9.5 Hz, 1H, CHCHaHb); ¹³C NMR ([D₆]DMSO): δ 170.96 (C, C=O), 138.02 (CH, imid), 136.64 (C, Ar), 135.41 (C, Ar), 133.40 (C, C−Cl), 132,69 (C, C−Cl), 132.63 (C, C−Cl), 130.24 (CH, Ar), 130.19 (2×CH, Ar), 129.00 (CH, Ar), 128.94 (2×CH, Ar), 128.74 (CH, imid), 127.57 (CH, Ar), 119.92 (CH, imidazole), 52.47 (CHCH₂), 48.68 (CHCH₂), 40.58 (NHCH₂); HRMS (ESI), m/z calcd for C₁₉H₁₇Cl₃N₃O ([M+H]⁺), 408.0438; found: 408.0432; HPLC (Method A): 99.6 %, t_R=4.56 min. 2‐(4‐Chlorophenyl)‐N‐(2,4‐dichlorobenzyl)acrylamide (6 f) was obtained as a white solid, yield 0.19 g (37 %); m.p. 104–106 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.87; ¹H NMR ([D₆]DMSO): δ 8.81 (t, J=5.8 Hz, 1H, NH), 7.62 (d, J=2.1 Hz, 1H, Ar), 7.46 (dd, J=8.9, 16.3 Hz, 5H, Ar), 7.39 (d, J=8.3 Hz, 1H, Ar), 5.88 (s, 1H, C=CHaHb), 5.80 (s, 1H, C=CHaHb), 4.43 (d, J=5.9 Hz, 2H, NHCH₂); ¹³C NMR ([D₆]DMSO): δ 168.43 (C, C=O), 143.97 (C, C=CH₂), 135.91 (C, Ar), 135.88 (C, C−Cl), 133.41 (C, C−Cl), 133.30 (C, C−Cl), 132.69 (C, Ar), 130.60 (CH, Ar), 129.49 (2×CH, Ar), 129.07 (CH, Ar), 128.81 (2×CH, Ar), 127.86 (CH, Ar), 119.69 (C=CH₂), 40.49 (NHCH₂); HRMS (ESI), m/z calcd for C₁₆H₁₂Cl₃NONa ([M+Na]⁺), 361.9882; found: 361.9880.
3‐(1H‐Imidazol‐1‐yl)‐N‐(4‐methylbenzyl)‐2‐phenylpropanamide (5 g, R¹=4‐CH₃, R²=H) andN‐(4‐methylbenzyl)‐2‐phenylacrylamide (6 g, R¹=4‐CH₃, R²=H). Prepared from 3‐((4‐methylbenzyl)amino)‐3‐oxo‐2‐phenylpropyl methanesulfonate (4 g; 0.7 g, 2.0 mmol) and purified by gradient column chromatography eluting the alkene (6 g) with petroleum ether/EtOAc 70 : 30 v/v, followed by the imidazole (5 g) with CH₂Cl₂/MeOH 90 : 10 v/v. 3‐(1H‐Imidazol‐1‐yl)‐N‐(4‐methylbenzyl)‐2‐phenylpropanamide (5 g) was obtained as a cream solid, yield 0.03 g (5 %); m.p. 134–136 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v), R_f=0.0; ¹H NMR ([D₆]acetone): δ 7.72 (brs, 1H, NH), 7.52 (brs, 1H, imid.), 7.44 (d, J=7.0 Hz, 2H, Ar), 7.32 (m, 3H, Ar), 7.11 (brs, 1H, imid.), 7.04 (d, J=7.9 Hz, 2H, Ar), 6.95 (d, J=8.0 Hz, 2H, Ar), 6.91 (brs, 1H, imid.), 4.76 (dd, J=9.3, 13.6 Hz, 1H, CHCHaHb), 4.37 (dd, J=6.2, 14.8 Hz, 1H, NHCHaHb), 4.28 (dd, J=5.7, 13.6 Hz, 1H, CHCHaHb), 4.23 (dd, J=5.6, 15.0 Hz, 1H, NHCHaHb), 4.09 (dd, J=5.7, 9.3 Hz, 1H, CHCHaHb), 2.27 (s, 3H, CH₃); ¹³C NMR ([D₆]acetone): δ 170.50 (C, C=O), 137.77 (C, Ar), 136.18 (C, Ar), 136.01 (C, Ar), 128.80 (2×CH, Ar), 128.55 (3×CH, Ar (2) and imid (1)), 128.39 (CH, imid), 127.98 (3×CH, Ar (2) and imid (1)), 127.48 (2×CH, Ar), 127.18 (2×CH, Ar), 54.00 (CHCH₂imid), 49.20 (CHCH₂imid), 42.24 (NHCH₂) 20.10 (CH₃); HRMS (ESI), m/z calcd for C₂₀H₂₂N₃O ([M+H]⁺), 320.1786; found: 320.1757; HPLC (Method A): 95.5 %, t_R=2.49 min. N‐(4‐Methylbenzyl)‐2‐phenylacrylamide (6 g) was obtained as an off‐white solid, yield 0.38 g (59 %); m.p. 92–94 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v), R_f=0.78; ¹H NMR ([D₆]DMSO): δ 8.69 (t, J=6.0 Hz, 1H, NH), 7.43 (m, 2H, Ar), 7.35 (m, 3H, Ar), 7.20 (d, J=8.0 Hz, 2H, Ar), 7.15 (d, J=7.9 Hz, 2H, Ar), 5.78 (s, 1H, C=CHaHb), 5.66 (s, 1H, C=CHaHb), 4.35 (d, J=6.1 Hz, 2H, NHCH₂), 2.29 (s, 3H, CH₃); ¹³C NMR ([D₆]DMSO): δ 168.63 (C, C=O), 145.68 (C, C=CH₂), 137.19 (C, Ar), 137.04 (C, Ar), 136.23 (C, Ar), 129.31 (2×CH, Ar),128.78 (2×CH, Ar), 128.55 (CH, Ar), 127.63 (2×CH, Ar), 127.50 (2×CH, Ar), 118.06 (C=CH₂), 42.54 (NHCH₂), 21.14 (CH₃); elemental analysis calcd (%) for C₁₇H₁₇NO (251.3274): C 81.24, H 6.82, N 5.57; found: C 81.35, H 7.06, N 5.53.
3‐(1H‐Imidazol‐1‐yl)‐2‐phenyl‐N‐(4‐(trifluoromethyl)benzyl)propanamide (5 h, R¹=4‐CF₃, R²=H) and 2‐phenyl‐N‐(4‐(trifluoromethyl)benzyl)acrylamide (6 h, R¹=4‐CF₃, R²=H). Prepared from 3‐oxo‐2‐phenyl‐3‐((4‐(trifluoromethyl)benzyl)amino)propyl methanesulfonate (4 h; 0.58 g, 1.44 mmol) and purified by gradient column chromatography eluting the alkene (6 h) with petroleum ether/EtOAc 70 : 30 v/v, followed by the imidazole (5 h) with CH₂Cl₂/MeOH 90 : 10 v/v. 3‐(1H‐Imidazol‐1‐yl)‐N‐(4‐(trifluoromethyl)benzyl)‐2‐phenylpropanamide (5 h) was obtained as a brown amorphous solid, yield 0.02 g (4 %); TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.0; ¹H NMR ([D₆]acetone): δ 7.87 (brs, 1H, NH), 7.50 (m, 4H, Ar (3) and imid. (1)), 7.33 (m, 2H, Ar (1) and imid. (1)), 7.21 (m, 4H, Ar (3) and imid. (1)), 7.11 (m, 2H, Ar), 4.67 (dd, J=9.8, 12.8 Hz, 1H, CHCHaHb), 4.38 (dd, J=6.2, 15.6 Hz, 1H, NHCHaHb), 4.22 (d, J=5.3 Hz, 1H, CHCHaHb), 4.20 (t, J=5.2 Hz, 1H, NHCHaHb), 4.05 (dd, J=5.3, 8.9 Hz, 1H, CHCHaHb); ¹³C NMR ([D₆]acetone): δ 170.85 (C, C=O), 143.94 (C, Ar), 137.47 (C, Ar), 128.64 (3×CH, Ar), 128.31 (CH, imid), 128.28 (C, Ar), 128.25 (CH, imid), 127.99 (3×CH, Ar), 127.63 (CH, Ar), 127.60 (2×CH, Ar), 127.49 (CH, imid), 125.07 & 125.04 (CF₃), 53.82 (CHCH₂imid), 49.89 (CHCH₂imid), 42.03 (NHCH₂); ¹⁹F NMR ([D₆]acetone): δ −62.87; HRMS (ESI), m/z calcd for C₂₀H₁₉F₃N₃O ([M+H]⁺), 374.1506; found: 374.1475; HPLC (Method A): 97.7 %, t_R=3.47 min. 2‐Phenyl‐N‐(4‐(trifluoromethyl)benzyl)acrylamide (6 h) was obtained as an off‐white solid, yield 0.32 g (59 %); m.p. 88–90 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.74; ¹H NMR ([D₆]DMSO): δ 8.83 (t, J=6.0 Hz, 1H, NH), 7.72 (d, J=8.1 Hz, 2H, Ar), 7.54 (d, J=8.0 Hz, 2H, Ar), 7.43 (d, J=6.8 Hz, 2H, Ar), 7.36 (m, 3H, Ar), 5.81 (s, 1H, C=CHaHb), 5.73 (s, 1H, C=CHaHb), 4.48 (d, J=6.1 Hz, 2H, NHCH₂); ¹³C NMR ([D₆]DMSO): δ 168.81 (C, C=O), 145.46 (C, =C=), 144.97 (C, Ar), 137.10 (C, Ar), 128.81 (2×CH, Ar), 128.61 (CH, Ar), 128.30 (3×CH, Ar), 127.80 (C, Ar), 127.57 (3×CH, Ar), 125.69 & 125.66 (CF₃), 118.60 (C=CH₂), 42.55 (NHCH₂); ¹⁹F NMR ([D₆]DMSO): δ −60.78; elemental analysis calcd (%) for C₁₇H₁₄F₃NO⋅0.1 H₂O (307.10042): C 66.49, H 4.66, N 4.56; found: C 66.43, H 4.75, N 4.48.
3‐(1H‐Imidazol‐1‐yl)‐N‐(4‐methoxybenzyl)‐2‐phenylpropanamide (5 i, R¹=4‐OCH₃, R²=H) andN‐(4‐methoxybenzyl)‐2‐phenylacrylamide (6 i, R¹=4‐OCH₃, R²=H). Prepared from 3‐((4‐methoxybenzyl)amino)‐3‐oxo‐2‐phenylpropyl methanesulfonate (4 i; 0.67 g, 1.85 mmol) and purified by gradient column chromatography eluting the alkene (6 i) with petroleum ether/EtOAc 60 : 40 v/v, followed by the imidazole (5 i) with CH₂Cl₂/MeOH 90 : 10 v/v. 3‐(1H‐Imidazol‐1‐yl)‐N‐(4‐methoxybenzyl)‐2‐phenylpropanamide (5 i) was obtained as a brown solid, yield 0.17 g (27 %); m.p. 102–104 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.0; ¹H NMR ([D₆]DMSO): δ 8.52 (t, J=5.8 Hz, 1H, NH), 7.53 (brs, 1H, imid), 7.39 (d, J=7.2 Hz, 2H, Ar), 7.34 (t, J=7.4 Hz, 2H, Ar), 7.28 (t, J=7.2 Hz, 1H, Ar), 7.09 (brs, 1H, imid), 6.93 (d, J=8.6 Hz, 2H, Ar), 6.87 (brs, 1H, imid), 6.79 (d, J=8.6 Hz, 1H, Ar), 4.62 (dd, J=9.6, 13.4 Hz, 1H, CHCHaHb), 4.24 (ϕt, J=5.6, 4.3 Hz, 1H, NHCHaHb), 4.22 (t, J=5.8 Hz, 1H, CHCHaHb), 4.06 (dd, J=5.4, 14.9 Hz, 1H, NHCHaHb), 4.00 (dd, J=5.8, 9.5 Hz, 1H, CHCHaHb), 3.71 (s, 3H, CH₃); ¹³C NMR ([D₆]DMSO): δ 170.89 (C, C=O), 158.64 (C, C‐OCH₃), 138.05 (C, Ar), 131.30 (C, Ar), 128.90 (2×CH, Ar (1) and imid (1)), 128.77 (2×CH, Ar (1) and imid (1)), 128.28 (2×CH, Ar (1) and imid (1)), 127.81 (CH, Ar), 114.05 (2×CH, Ar), 55.52 (OCH₃), 53.31 (CHCH₂imid), 48.91 (CHCH₂imid), 41.99 (NHCH₂); LRMS (ES+TOF, m/z): 336.17 [C₂₀H₂₁N₃O₂+H]⁺; HRMS (ES+TOF), m/z calcd for C₂₀H₂₂N₃O₂ ([M+H]⁺), 336.1712; found: 336.1715; HPLC (Method A): 95.9 %, t_R=5.07 min. N‐(4‐Methoxybenzyl)‐2‐phenylacrylamide (6 i) was obtained as an off‐white solid, yield 0.31 g (50 %); m.p. 100–102 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.64; ¹H NMR ([D₆]DMSO): δ 8.66 (t, J=5.9 Hz, 1H, NH), 7.43 (d, J=4.7 Hz, 2H, Ar), 7.36 (m, 3H, Ar), 7.25 (d, J=8.7 Hz, 2H, Ar), 6.91 (d, J=8.7 Hz, 2H, Ar), 5.77 (s, 1H, C=CHaHb), 5.65 (s, 1H, C=CHaHb), 4.33 (d, J=6.1 Hz, 2H, NHCH₂), 3.75 (s, 3H, CH₃); ¹³C NMR ([D₆]DMSO): δ 168.58 (C, C=O), 158.66 (C, C‐OCH₃), 145.72 (C, C=CH₂), 137.22 (C, Ar), 132.02 (C, Ar), 129.00 (2×CH, Ar), 128.78 (2×CH, Ar), 128.54 (CH, Ar), 127.50 (2×CH, Ar), 118.04 (C=CH₂), 114.18 (2×CH, Ar), 55.53 (CH₃), 42.27 (NHCH₂); elemental analysis calcd (%) for C₁₇H₁₇NO₂ (267.3268): C 76.38, H 6.41, N 5.24; found: C 76.35, H 6.30, N 5.13.
N‐(3,4‐Dimethoxybenzyl)‐3‐(1H‐imidazol‐1‐yl)‐2‐phenylpropanamide (5 j, R¹=3,4‐diOCH₃, R²=H) andN‐(3,4‐dimethoxybenzyl)‐2‐phenylacrylamide (6 j, R¹=3,4‐diOCH₃, R²=H). Prepared from 3‐((3,4‐dimethoxybenzyl)amino)‐3‐oxo‐2‐phenylpropyl methanesulfonate (4 j; 0.52 g, 1.30 mmol) and purified by gradient column chromatography eluting the alkene (6 j) with petroleum ether/EtOAc 60 : 40 v/v, followed by the imidazole (5 j) with CH₂Cl₂/MeOH 90 : 10 v/v. N‐(3,4‐Dimethoxybenzyl)‐3‐(1H‐imidazol‐1‐yl)‐2‐phenylpropanamide (5 j) was obtained as a pale yellow oil, yield 0.25 g (51 %); TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.0; ¹H NMR ([D₆]DMSO): δ 8.55 (t, J=5.8 Hz, 1H, NH), 7.53 (brs, 1H, imid), 7.41 (d, J=7.2 Hz, 2H, Ar), 7.34 (t, J=7.4 Hz, 2H, Ar), 7.28 (t, J=7.3 Hz, 1H, Ar), 7.09 (brs, 1H, imid), 6.85 (brs, 1H, imid), 6.80 (d, J=8.2 Hz, 1H, Ar), 6.60 (d, J=1.8 Hz, 1H, Ar), 6.56 (dd, J=1.8, 8.2 Hz, 1H, Ar), 4.64 (dd, J=9.6, 13.5 Hz, 1H, CHCHaHb), 4.23 (dd, J=7.5, 13.5 Hz, 1H, CHCHaHb), 4.16 (d, J=5.8 Hz, 2H, NHCHaHb), 4.01 (dd, J=5.7, 9.5 Hz, 1H, CHCHaHb), 3.70 (s, 3H, CH₃), 3.58 (s, 3H, CH₃); ¹³C NMR ([D₆]DMSO): δ 170.93 (C, C=O), 149.10 (C, COCH₃), 148.17 (C, COCH₃), 138.16 (C, Ar), 131.88 (C, Ar), 128.93 (3×CH, Ar (2) and imid (1)), 128.52 (CH, imid), 128.27 (3×CH, Ar (2) and imid (1)), 127.81 (CH, Ar), 119.55 (CH, Ar), 112.05 (CH, Ar), 111.14 (CH, Ar), 56.02 (OCH₃), 55.67 (OCH₃), 53.35 (CHCH₂imid), 48.80 (CHCH₂imid), 42.21 (NHCH₂); LRMS (ES+TOF, m/z): 366.18 [C₂₁H₂₃N₃O₃ + H]⁺; HRMS (ES+ TOF), m/z calcd for C₂₁H₂₄N₃O₃ ([M+H]⁺), 366.1818; found: 366.1826; HPLC (Method A): 99.9 %, t_R=4.81 min. N‐(3,4‐Dimethoxybenzyl)‐2‐phenylacrylamide (6 j) was obtained as white solid, yield 0.09 g (23 %); m.p. 102–104 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.64; ¹H NMR ([D₆]DMSO): δ 8.66 (t, J=6.0 Hz, 1H, NH), 7.44 (m, 2H, Ar), 7.36 (m, 3H, Ar), 6.92 (m, 2H, Ar), 6.84 (dd, J=1.9, 8.2 Hz, 1H, Ar), 5.78 (s, 1H, C=CHaHb), 5.65 (s, 1H, C=CHaHb), 4.33 (d, J=6.1 Hz, 2H, NHCH₂), 3.75 (s, 3H, CH₃), 3.74 (s, 3H, CH₃); ¹³C NMR ([D₆]DMSO): δ 168.68 (C, C=O), 149.13 (C, C‐OCH₃), 148.21 (C, C‐OCH₃), 145.75 (C, C=CH₂), 137.19 (C, Ar), 132.52 (C, Ar), 128.79 (2×CH, Ar), 128.57 (CH, Ar), 127.45 (2×CH, Ar), 119.74 (CH, Ar), 117.87 (C=CH₂), 112.24 (CH, Ar), 111.69 (CH, Ar), 56.05 (CH₃), 55.86 (CH₃), 42.54 (NHCH₂); elemental analysis calcd (%) for C₁₈H₁₉NO₃ (299.3530): C 72.71, H 6.44, N 4.71; found: C 72.59, H 6.46, N 4.82.
N‐(4‐Chlorobenzyl)‐2‐phenyl‐3‐(1H‐1,2,4‐triazol‐1‐yl)propanamide (5 k, R¹=4‐Cl, R²=H). Prepared from 3‐((4‐chlorobenzyl)amino)‐3‐oxo‐2‐phenylpropyl methanesulfonate (4 c; 0.59 g, 1.61 mmol) and purified by gradient column chromatography eluting the triazole (5 k) with petroleum ether/EtOAc 10 : 90 v/v. Product was obtained as a white solid, yield 0.22 g (40 %); m.p. 113–115 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.0; ¹H NMR ([D₆]DMSO): δ 8.72 (t, J=6.0 Hz, 1H, NH), 8.32 (s, 1H, triaz), 7.99 (s, 1H, triaz), 7.20 (m, 5H, Ar), 7.28 (d, J=8.4 Hz, 2H, Ar), 6.97 (d, J=8.5 Hz, 2H, Ar), 4.83 (dd, J=9.2, 13.8 Hz, 1H, CHCHaHb), 4.44 (dd, J=6.5, 13.5 Hz, 1H, CHCHaHb), 4.27 (m, 2H, CHCHaHb+NHCHaHb), 4.08 (dd, J=5.5, 15.6 Hz, NHCHaHb); ¹³C NMR ([D₆]DMSO): δ 170.74 (C, C=O), 151.99 (CH, triaz), 145.08 (CH, triaz), 138.58 (C, Ar), 137.94 (C, C−Cl), 137.47 (C, C−Cl), 131.68 (C, Ar), 129.9.36 (CH, Ar), 129.07 (2×CH, Ar), 129.02 (2×CH, Ar), 128.78 (CH, Ar), 128.54 (2×CH, Ar), 128.23 (CH, Ar), 51.56 (CHCH₂triaz), 51.10 (CHCH₂triaz), 41.72 (NHCH₂); elemental analysis calcd (%) for C₁₈H₁₇ClN₄O (340.8115): C 63.44; H, 5.03; N, 16.43 ; found: C 63.22; H, 5.01; N, 16.33; HPLC (Method A): 99.7 %, t_R=4.91 min.
tert‐Butyl (4‐((2‐phenyl‐3‐(1H‐1,2,4‐triazol‐1‐yl)propanamido)methyl)phenyl)carbamate (5 l, R¹=NHBoc, R²=H) andtert‐butyl (4‐((2‐phenylacrylamido)methyl)phenyl)carbamate (6 l, R¹=NHBoc, R²=H). Prepared from 3‐((4‐((tert‐butoxycarbonyl)amino)benzyl)amino)‐3‐oxo‐2‐phenylpropyl methanesulfonate (4 k; 0.62 g, 1.39 mmol) and purified by gradient column chromatography eluting the alkene (6 l) with petroleum ether/EtOAc 60 : 40 v/v, followed by the imidazole (5 l) with CH₂Cl₂/MeOH 90 : 10 v/v. tert‐Butyl (4‐((2‐phenyl‐3‐(1H‐1,2,4‐triazol‐1‐yl)propanamido)methyl)phenyl)carbamate (5 l) was obtained as a pale yellow oil, yield 0.49 g (84 %); TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.0; ¹H NMR (CDCl₃): δ 7.80 (s, 1H, triazole), 7.76 (s, 1H, triazole), 7.18 (m, 7H, Ar), 6.81 (d, J=8.5 Hz, 2H, Ar), 6.61 (s, 1H, NH), 6.10 (t, J=5.6 Hz, 1H, NHCHaHb), 4.83 (dd, J=8.7, 13.6 Hz, 1H, CHCHaHb), 4.23 (ddd, J=6.1, 14.7, 21.0 Hz, 2H, CHCHaHb and NHCHaHb), 4.11 (dd, J=5.5, 9.2, 14.8 Hz, 1H, NHCHaHb), 3.97 (dd, J=6.2, 8.7 Hz, 1H, CHCHaHb), 1.39 (s, 9H, C(CH₃)₃); ¹³C NMR (CDCl₃): δ 170.26 (C, C=O), 152.79 (C, C=O), 151.99 (CH, triaz), 144.21 (CH, triaz), 137.77 (C, Ar), 135.96 (C, Ar), 132.12 (C, Ar), 129.25 (2×CH, Ar), 128.35 (CH, Ar), 128.14 (3×CH, Ar), 127.81 (2×CH, Ar), 118.75 (CH, Ar), 80.60 (C(CH₃)₃), 54.71 (CHCH₂), 52.05 (CHCH₂), 42.15 (NHCH₂), 28.33 (C(CH₃)₃); HRMS (ESI), m/z calcd for C₂₃H₂₈N₅O₃ ([M+H]⁺), 422.2218; found: 422.2187; HPLC (Method A): 99.7 %, t_R=4.82 min. tert‐Butyl (4‐((2‐phenylacrylamido)methyl)phenyl)carbamate (6 l) was obtained as white solid, yield 0.06 g (9 %); m.p. 136–138 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.7; ¹H NMR (CDCl₃): δ 7.38 (m, 5H, Ar), 7.33 (d, J=8.5 Hz, 2H, Ar), 7.21 (d, J=8.5 Hz, 2H, Ar), 6.53 (s, 1H, NH), 6.21 (d, J=1.3 Hz, 1H, C=CHaHb), 5.97 (brs, 1H, NH), 5.65 (d, J=1.3 Hz, 1H, C=CHaHb), 4.49 (d, J=5.6 Hz, 2H, NHCH₂), 1.53 (s, 9H, C(CH₃)₃); ¹³C NMR (CDCl₃): δ 167.07 (C, C=O), 152.73 (C, C=O), 144.61 (C, C=CHaHb), 137.77 (C, Ar), 136.97 (C, Ar), 132.60 (C, Ar), 128.77 (2×CH, Ar), 128.57 (CH, Ar), 128.50 (3×CH, Ar), 128.82 (2×CH, Ar), 122.64 (C=CH₂), 118.78 (CH, Ar), 80.64 (C(CH₃)₃), 43.46 (NHCH₂), 28.34 (C(CH₃)₃); HRMS (ESI), m/z calcd for C₂₁H₂₅N₂O₃ ([M+H]⁺), 353.1876; found: 353.1860.
N‐(4‐Chlorobenzyl)‐2‐phenylacrylamide (6 c, R¹=4‐Cl, R²=H). Prepared from 3‐((4‐chlorobenzyl)amino)‐3‐oxo‐2‐phenylpropyl methanesulfonate (4 c; 0.38 g, 1.03 mmol) and purified by gradient column chromatography eluting the alkene (6 c) with petroleum ether/EtOAc 70 : 30 v/v. Product was obtained as a white solid, yield 0.09 g (23 %); m.p. 118–120 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.75; ¹H NMR ([D₆]DMSO): δ 8.76 (t, J=5.9 Hz, 1H, NH), 7.38 (m, 9H, Ar), 5.79 (s, 1H, C=CHaHb), 5.69 (s, 1H, C=CHaHb), 4.37 (d, J=6.1 Hz, 2H, NHCH₂; ¹³C NMR ([D₆]DMSO): δ 168.72 (C, C=O), 145.53 (C, C=CH₂), 139.13 (C, Ar), 137.12 (C, Ar), 131.77 (C, C−Cl), 129.54 (2×CH, Ar), 128.80 (2×CH, Ar), 128.73 (2×CH, Ar), 128.59 (CH, Ar), 127.54 (2×CH, Ar), 118.40 (C=CH₂), 42.22 (NHCH₂); elemental analysis calcd (%) for C₁₆H₁₄ClNO (271.7457): C 70.72, H 5.19, N 5.15; found: C 70.44, H 5.16, N 5.04.
2‐Phenyl‐N‐(4‐(phenylsulfonamido)benzyl)‐3‐(1H‐1,2,4‐triazol‐1‐yl)propanamide (12 a, R¹=H) and 2‐phenyl‐N‐(4‐(phenylsulfonamido)benzyl) acrylamide (13 a, R¹=H). Prepared from 3‐oxo‐2‐phenyl‐3‐((4‐(phenylsulfonamido)benzyl)amino)propyl methanesulfonate (11 a; 0.32 g, 0.65 mmol) and purified by gradient column chromatography eluting the alkene (13 a) with petroleum ether/EtOAc 40 : 60 v/v, followed by the triazole (12 a) with CH₂Cl₂/MeOH 90 : 10 v/v. 2‐Phenyl‐N‐(4‐(phenylsulfonamido)benzyl)‐3‐(1H‐1,2,4‐triazol‐1‐yl)propanamide (12 a) was obtained as a white solid, yield 0.06 g (19 %); m.p. 96–98 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.0; ¹H NMR ([D₆]DMSO): δ 10.20 (brs, 1H, NHSO₂), 8.58 (t, J=5.9 Hz, 1H, NH), 8.30 (s, 1H, triazole), 7.92 (s, 1H, triazole), 7.73 (d, J=7.1 Hz, 2H, Ar), 7.61 (t, J=7.4 Hz, 1H, Ar), 7.54 (t, J=7.5 Hz, 2H, Ar), 7.31 (m, 5H, Ar), 6.93 (d, J=8.6 Hz, 2H, Ar), 6.79 (d, J=8.6 Hz, 2H, Ar), 4.80 (dd, J=9.1, 13.5 Hz, 1H, CHCHaHb), 4.42 (dd, J=6.6, 13.5 Hz, 1H, CHCHaHb), 4.18 (ddd, J=6.5, 15.4, 20.9 Hz, 2H, CHCHaHb+NHCHaHb), 3.97 (dd, J=5.8, 15.4 Hz, 1H, NHCHaHb); ¹³C NMR ([D₆]DMSO): δ 170.59 (C, C=O), 151.89 (CH, triazole), 145.63 (CH, triazole), 139.93 (C, Ar), 137.50 (C, Ar), 136.68 (C, Ar), 135.23 (C, Ar), 133.33 (CH, Ar), 129.70 (2×CH, Ar), 128.96 (2×CH, Ar), 128.21 (2×CH, Ar), 128.05 (2×CH, Ar), 127.91 (CH, Ar), 127.09 (2×CH, Ar), 120.51 (2×CH, Ar), 51.52 (CHCH₂), 51.08 (CHCH₂), 41.78 (NHCH₂); HRMS (ESI), m/z calcd for C₂₄H₂₄N₅O₃S ([M+H]⁺), 462.1594; found: 462.1613; HPLC (Method A): 99.9 %, t_R=4.68 min. 2‐Phenyl‐N‐(4‐(phenylsulfonamido)benzyl) acrylamide (13 a) was obtained as white waxy solid, yield 0.15 g (51 %); TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.46; ¹H NMR ([D₆]DMSO): δ 10.25 (brs, 1H, NHSO₂), 8.63 (t, J=6.0 Hz, 1H, NH), 7.77 (d, J=7.1 Hz, 2H, Ar), 7.60 (t, J=7.1 Hz, 1H, Ar), 7.54 (t, J=7.45 Hz, 2H, Ar), 7.36 (m, 5H, Ar), 7.16 (d, J=8.6 Hz, 2H, Ar), 7.06 (d, J=8.6 Hz, 2H, Ar), 5.76 (s, 1H, C=CHaHb), 5.64 (s, 1H, C=CHaHb), 4.27 (d, J=6.1 Hz, 2H, NHCH₂); ¹³C NMR ([D₆]DMSO): δ 168.65 (C, C=O), 145.56 (C, C=CH₂), 140.00 (C, Ar), 137.13 (C, Ar), 136.71 (C, Ar), 135.84 (C, Ar), 133.33 (CH, Ar), 129.71 (2×CH, Ar), 128.77 (2×CH, Ar), 128.55 (CH, Ar), 128.42 (2×CH, Ar), 127.49 (2×CH, Ar), 127.11 (2×CH, Ar), 120.69 (2×CH, Ar), 118.18 (C=CH₂), 42.21 (NHCH₂); HRMS (ESI), m/z calcd for C₂₂H₂₁N₂O₃S ([M+H]⁺), 393.1267; found: 393.1255.
N‐(4‐((4‐Fluorophenyl)sulfonamido)benzyl)‐2‐phenyl‐3‐(1H‐1,2,4‐triazol‐1‐yl) propanamide (12 b, R¹=4‐F) andN‐(4‐((4‐fluorophenyl)sulfonamido)benzyl)‐2‐phenylacrylamide (13 b, R¹=4‐F). Prepared from 3‐oxo‐2‐phenyl‐3‐((4‐(4‐fluorophenylsulfonamido)benzyl)amino)propyl methanesulfonate (11 b; 0.31 g, 0.62 mmol) and purified by gradient column chromatography eluting the alkene (13 b) with petroleum ether/EtOAc 50 : 50 v/v, followed by the triazole (12 b) with CH₂Cl₂/MeOH 90 : 10 v/v. N‐(4‐((3‐Fluorophenyl)sulfonamido)benzyl)‐2‐phenyl‐3‐(1H‐1,2,4‐triazol‐1‐yl) propanamide (12 b) was obtained as a white solid, yield 0.09 g (30 %); m.p. 78–80 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.0; ¹H NMR ([D₆]DMSO): δ 10.21 (brs, 1H, NHSO₂), 8.59 (t, J=5.9 Hz, 1H, NH), 8.31 (s, 1H, triazole), 7.93 (s, 1H, triazole), 7.79 (dd, J=5.2, 8.9 Hz, 2H, Ar), 7.34 (m, 7H, Ar), 6.93 (d, J=8.5 Hz, 2H, Ar), 6.81 (d, J=8.5 Hz, 2H, Ar), 4.81 (dd, J=9.1, 13.5 Hz, 1H, CHCHaHb), 4.43 (dd, J=6.6, 13.5 Hz, 1H, CHCHaHb), 4.19 (m, 2H, CHCHaHb+NHCHaHb), 3.99 (dd, J=5.4, 15.4 Hz, 1H, NHCHaHb); ¹³C NMR ([D₆]DMSO): δ 170.60 (C, C=O), 165.73 (C, Ar), 163.73 (C, Ar), 151.90 (CH, triazole), 143.33 (CH, triazole), 137.51 (C, Ar), 136.49 (C, Ar), 135.48 (C, Ar), 130.21 (CH, Ar), 130.13 (CH, Ar), 128.96 (2×CH, Ar), 128.22 (2×CH, Ar), 128.08 (2×CH, Ar), 127.90 (CH, Ar), 120.76 (2×CH, Ar), 117.00 (CH, Ar), 116.82 (CH, Ar), 51.53 (CHCH₂), 51.09 (CHCH₂), 41.78 (NHCH₂); elemental analysis calcd (%) for C₂₄H₂₂FN₅O₃S⋅0.1 H₂O (481.32942): C 59.89, H 4.65, N 14.55; found: C 59.52, H 4.49, N 14.26; HPLC (Method A): 99.9 %, t_R=4.69 min. N‐(4‐((4‐Fluorophenyl)sulfonamido)benzyl)‐2‐phenylacrylamide (13 b) was obtained as a white solid, yield 0.12 g (41 %); m.p. 136–138 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.5; ¹H NMR ([D₆]DMSO): δ 10.27 (brs, 1H, NHSO₂), 8.64 (t, J=6.1 Hz, 1H, NH), 7.81 (dd, J=5.2, 9.0 Hz, 2H, Ar), 7.36 (m, 7H, Ar), 7.17 (d, J=8.6 Hz, 2H, Ar), 7.06 (d, J=8.6 Hz, 2H, Ar), 5.76 (s, 1H, C=CHaHb), 5.64 (s, 1H, C=CHaHb), 4.28 (d, J=6.1 Hz, 2H, NHCH₂); ¹³C NMR ([D₆]DMSO): δ 168.65 (C, C=O), 165.73 (C, Ar), 163.73 (C, Ar), 145.56 (C, C=CH₂), 137.13 (C, Ar), 136.50 (C, Ar), 136.09 (C, Ar), 130.22 (CH, Ar), 130.15 (CH, Ar), 128.76 (2×CH, Ar), 128.54 (CH, Ar), 128.47 (2×CH, Ar), 127.49 (2×CH, Ar), 120.93 (2×CH, Ar), 118.20 (C=CH₂), 117.02 (CH, Ar), 116.84 (CH, Ar), 42.20 (NHCH₂); HRMS (ESI), m/z calcd for C₂₂H₂₀FN₂O₃S ([M+H]⁺), 411.1173; found: 411.1173.
N‐(4‐((4‐Chlorophenyl)sulfonamido)benzyl)‐2‐phenyl‐3‐(1H‐1,2,4‐triazol‐1‐yl) propanamide (12 c, R¹=4‐Cl) andN‐(4‐((4‐chlorophenyl)sulfonamido)benzyl)‐2‐phenylacrylamide (13 c, R¹=4‐Cl). Prepared from 3‐((4‐((4‐chlorophenyl)sulfonamido)benzyl)amino)‐3‐oxo‐2‐phenylpropyl methanesulfonate (11 c; 0.20 g, 0.41 mmol) and purified by gradient column chromatography eluting the alkene (13 c) with petroleum ether/EtOAc 50 : 50 v/v, followed by the triazole (12 c) with CH₂Cl₂/MeOH 90 : 10 v/v. N‐(4‐((4‐Chlorophenyl)sulfonamido)benzyl)‐2‐phenyl‐3‐(1H‐1,2,4‐triazol‐1‐yl) propanamide (12 c) was obtained as an off‐white solid, yield 0.02 g (11 %); m.p. 122–124 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.0; ¹H NMR ([D₆]DMSO): δ 10.27 (brs, 1H, NHSO₂), 8.59 (t, J=5.9 Hz, 1H, NH), 8.31 (s, 1H, triazole), 7.92 (s, 1H, triazole), 7.72 (d, J=8.8 Hz, 2H, Ar), 7.63 (d, J=8.8 Hz, 2H, Ar), 7.30 (m, 5H, Ar), 6.92 (d, J=8.6 Hz, 2H, Ar), 6.81 (d, J=8.6 Hz, 2H, Ar), 4.81 (dd, J=9.1, 13.5 Hz, 1H, CHCHaHb), 4.43 (dd, J=6.6, 13.5 Hz, 1H, CHCHaHb), 4.19 (m, 2H, CHCHaHb+NHCHaHb), 3.99 (dd, J=5.4, 15.4 Hz, 1H, NHCHaHb); ¹³C NMR ([D₆]DMSO): δ 170.60 (C, C=O), 151.89 (CH, triazole), 143.81 (CH, triazole), 138.76 (C, Ar), 138.21 (C, C−Cl), 137.51 (C, Ar), 136.33 (C, Ar), 135.61 (C, Ar), 129.89 (2×CH, Ar), 129.07 (2×CH, Ar), 128.96 (2×CH, Ar), 128.22 (2×CH, Ar), 128.12 (2×CH, Ar), 127.90 (CH, Ar), 120.85 (2×CH, Ar), 51.52 (CHCH₂), 51.09 (CHCH₂), 41.78 (NHCH₂); HRMS (ESI), m/z calcd for C₂₄H₂₃ClN₅O₃S ([M+H]⁺), 455.1119; found: 455.1143; HPLC (Method A): 99.9 %, t_R=4.75 min. N‐(4‐((3‐Chlorophenyl)sulfonamido)benzyl)‐2‐phenylacrylamide (13 c) was obtained as a white solid, yield 0.10 g (50 %); m.p. 164–166 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.73; ¹H NMR ([D₆]DMSO): δ 10.33 (brs, 1H, NHSO₂), 8.64 (t, J=6.1 Hz, 1H, NH), 7.75 (d, J=8.8 Hz, 2H, Ar), 7.63 (d, J=8.8 Hz, 2H, Ar), 7.36 (m, 5H, Ar), 7.18 (d, J=8.5 Hz, 2H, Ar), 7.05 (d, J=8.5 Hz, 2H, Ar), 5.76 (s, 1H, C=CHaHb), 5.64 (s, 1H, C=CHaHb), 4.28 (d, J=6.1 Hz, 2H, NHCH₂); ¹³C NMR ([D₆]DMSO): δ 168.67 (C, C=O), 145.55 (C, C=CH₂), 138.81 (C, Ar), 138.22 (C, C−Cl), 137.12 (C, Ar), 136.20 (C, Ar), 129.90 (2×CH, Ar), 129.08 (2×CH, Ar), 128.77 (2×CH, Ar), 128.55 (CH, Ar), 128.51 (2×CH, Ar), 127.49 (2×CH, Ar), 121.02 (2×CH, Ar), 118.20 (C=CH₂), 42.21 (NHCH₂); HRMS (ESI), m/z calcd for C₂₂H₂₀ClN₂O₃S ([M+H]⁺), 427.0884; found: 427.0872.
2‐Phenyl‐N‐(4‐(4‐methoxyphenylsulfonamido)benzyl)‐3‐(1H‐1,2,4‐triazol‐1‐yl)propanamide (12 d, R¹=4‐OCH₃) and 2‐phenyl‐N‐(4‐(4‐methoxyphenylsulfonamido)benzyl)acrylamide (13 d, R¹=4‐OCH₃). Prepared from 3‐((4‐((4‐methoxyphenyl)sulfonamido)benzyl)amino)‐3‐oxo‐2‐phenylpropyl methanesulfonate (11 d; 0.40 g, 0.77 mmol) and purified by gradient column chromatography eluting the alkene (13 d) with petroleum ether/EtOAc 40 : 60 v/v, followed by the triazole (12 d) with CH₂Cl₂/MeOH 90 : 10, v/v. N‐(4‐((4‐Methoxyphenyl)sulfonamido)benzyl)‐2‐phenyl‐3‐(1H‐1,2,4‐triazol‐1‐yl) propanamide (12 d) was obtained as a white solid, yield 0.07 g (17 %); m.p. 160–162 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.0; ¹H NMR ([D₆]DMSO): δ 10.05 (brs, 1H, NHSO₂), 8.58 (t, J=5.9 Hz, 1H, NH), 8.31 (s, 1H, triazole), 7.92 (s, 1H, triazole), 7.67 (d, J=9.0 Hz, 2H, Ar), 7.31 (m, 5H, Ar), 7.05 (d, J=9.0 Hz, 2H, Ar), 6.93 (d, J=8.5 Hz, 2H, Ar), 6.79 (d, J=8.5 Hz, 2H, Ar), 4.81 (dd, J=9.0, 13.4 Hz, 1H, CHCHaHb), 4.43 (dd, J=6.6, 13.5 Hz, 1H, CHCHaHb), 4.19 (m, 2H, CHCHaHb+NHCHaHb), 3.98 (dd, J=5.4, 15.4 Hz, 1H, NHCHaHb), 3.80 (s, 3H, OCH₃); ¹³C NMR ([D₆]DMSO): δ 170.59 (C, C=O), 162.85 (C, C‐OCH₃), 151.84 (CH, triazole), 145.04 (CH, triazole), 137.57 (CH, Ar), 136.97 (C, Ar), 135.00 (C, Ar), 131.74 (C, Ar), 129.31 (2×CH, Ar), 128.93 (2×CH, Ar), 128.22 (2×CH, Ar), 128.02 (2×CH, Ar), 128.87 (CH, Ar), 120.36 (2×CH, Ar), 114.81 (2×CH, Ar), 56.09 (OCH₃), 51.58 (CHCH₂), 51.18 (CHCH₂), 41.87 (NHCH₂); HRMS (ESI), m/z calcd for C₂₅H₂₆N₅O₄S ([M+H]⁺), 492.1706; found: 492.1695; HPLC (Method A): 99.99 %, t_R=4.68 min. N‐(4‐((4‐Methoxyphenyl)sulfonamido)benzyl)‐2‐phenylacrylamide (13 d) was obtained as a white solid, yield 0.17 g (44 %); m.p. 98–100 °C; TLC (petroleum ether/EtOAc 1 : 1 v/v); R_f=0.33; ¹H NMR ([D₆]DMSO): δ 10.11 (brs, 1H, NHSO₂), 8.63 (t, J=6.1 Hz, 1H, NH), 7.69 (d, J=9.0 Hz, 2H, Ar), 7.38 (m, 5H, Ar), 8.65 (d, J=8.7 Hz, 2H, Ar), 7.05 (d, J=8.8 Hz, 4H, Ar), 5.76 (s, 1H, C=CHaHb), 5.64 (s, 1H, C=CHaHb), 4.27 (d, J=6.1 Hz, 2H, NHCH₂), 3.79 (s, 3H, OCH₃); ¹³C NMR ([D₆]DMSO): δ 168.65 (C, C=O), 162.84 (C, C‐OCH₃), 145.56 (C, C=CH₂), 136.97 (C, Ar), 135.57 (C, Ar), 131.64 (C, Ar), 129.34 (2×CH, Ar), 128.76 (2×CH, Ar), 128.54 (CH, Ar), 128.38 (2×CH, Ar), 127.49 (2×CH, Ar), 120.43 (2×CH, Ar), 118.16 (C=CH₂), 114.82 (2×CH, Ar), 56.07 (OCH₃), 42.21 (NHCH₂); HRMS (ESI), m/z calcd for C₂₃H₂₃N₂O₄S ([M+H]⁺), 423.1379; found: 423.1368.

Binjubair F.A., Parker J.E., Warrilow A.G., Puri K., Braidley P.J., Tatar E., Kelly S.L., Kelly D.E, & Simons C. (2020). Small‐Molecule Inhibitors Targeting Sterol 14α‐Demethylase (CYP51): Synthesis, Molecular Modelling and Evaluation Against Candida albicans. Chemmedchem, 15(14), 1294-1309.

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Publication 2020

Most recents protocols related to «Methyl carbamate»

Preparative Chiral HPLC Separation of Pyrazole-Imidazolidinone

Enantiomeric separation of 8.9 g of rac-tert-butyl{[4-(1-methyl-1H-pyrazol-5-yl)-2,5-dioxoimidazolidin-4-yl]methyl}carbamate
(41) was done using a preparative chiral HPLC method
(see Supporting Information for details).
Product containing samples were united, the solvents were evaporated
with a rotary evaporator, and the residue was lyophilized. 3.34 g
(100% purity, 38% yield) of the title compound was obtained. Chiral
HPLC (Column: Chiralpak AD-H 3 μm 100 × 4.6 mm²; solvent: 85% CO₂/15% methanol; flow: 3 mL/min; UV-detection:
210 nm): Rt = 1.618 min, 99.5% ee. LC–MS (Method 1): Rt = 0.53
min; MS (ESIpos): m/z = 310 [M +
H]⁺.

Meibom D., Wasnaire P., Beyer K., Broehl A., Cancho-Grande Y., Elowe N., Henninger K., Johannes S., Jungmann N., Krainz T., Lindner N., Maassen S., MacDonald B., Menshykau D., Mittendorf J., Sanchez G., Schaefer M., Stefan E., Torge A., Xing Y, & Zubov D. (2024). BAY-9835: Discovery of the First Orally Bioavailable ADAMTS7 Inhibitor. Journal of Medicinal Chemistry, 67(4), 2907-2940.

Publication 2024

Synthesis of 2-(5-Methyl-1,3-Thiazol-4-yl)Acetamide

In a microwave vial, tert-butyl [2-(5-methyl-1,3-thiazol-4-yl)-2-oxoethyl]carbamate
(980 mg, 25.88 mmol) was dissolved in 7 mL of methanol. Potassium
cyanide (996 mg, 15.29 mmol) and ammonium carbonate (1.47 g, 15.29
mmol) were added. The vial was sealed, and the mixture was stirred
at 40 °C for 2 d. More potassium cyanide (996 mg, 15.29 mmol)
and ammonium carbonate (1.47 g, 15.29 mmol) were added, and the reaction
mixture was stirred at 40 °C for 3 d. The reaction mixture was
concentrated. The residue was poured on Isolute and purified by column
chromatography. Product containing samples were united and the solvents
were evaporated. 766 mg (100% purity, 61% yield) of the title compound
was obtained. LC–MS (Method 2): Rt = 1.09 min; MS (ESIpos): m/z = 325 [M – H]⁺.

Publication 2024

Synthesis of 2-(1-Methyl-1H-pyrazol-5-yl)acetamide

Divided in five microwave vials (30 mL
volume vials): tert-butyl [2-(1-methyl-1H-pyrazol-5-yl)-2-oxoethyl]carbamate
(40) (10.0 g, 85% purity, 35.52 mmol) was dissolved in
60 mL of methanol. Potassium cyanide (10.89 g, 167.17 mmol) and ammonium
carbonate (16.06 g, 167.17 mmol) were added. The vials were sealed,
and the mixture was stirred at 80 °C for 2 d. The contents of
the vials were pooled, the salts were filtered off and rinsed with
methanol, and the filtrate was concentrated. The residue was purified
by column chromatography (Machine: Biotage Isolera; column: Biotage
SNAP Ultra 100 g; eluent: DCM/MeOH: 5% MeOH → 30% MeOH; flow:
100 mL/min). Product containing samples were united and the solvents
were evaporated. 8.9 g (100% purity, 81% yield) of the title compound
was obtained. LC–MS (Method 2): Rt = 0.95 min; MS (ESIpos): m/z = 310 [M – H]⁺.

Publication 2024

Synthesis of 2-Amino-5-methyl-2-(pyridin-3-yl)thiazole

In a microwave vial, tert-butyl {2-[5-methyl-2-(pyridin-3-yl)-1,3-thiazol-4-yl]-2-oxoethyl}carbamate
(4.29 g, 12.87 mmol) was dissolved in 30 mL of methanol. Potassium
cyanide (3.35 g, 51.47 mmol) and ammonium carbonate (4.95 g, 51.47
mmol) were added. The vial was sealed, and the mixture was stirred
at 80 °C overnight. The salts were filtered off and rinsed with
methanol. The filtrate was concentrated. The crude product was purified
by preparative HPLC. Product containing samples were united, the solvents
were evaporated with a rotary evaporator and the residue was lyophilized.
1.97 g (100% purity, 38% yield) of the title compound was obtained.
LC–MS (Method 2): Rt = 1.21 min; MS (ESIpos): m/z = 404 [M + H]⁺.

Publication 2024

Pyrazole Synthesis via Cyanide Cyclization

In a microwave vial, tert-butyl [2-(4-methyl-1-phenyl-1H-pyrazol-3-yl)-2-oxoethyl]carbamate
(1.18 g, 84% purity, 3.14 mmol) was dissolved in 15 mL of methanol.
Potassium cyanide (1.46 g, 22.45 mmol) and ammonium carbonate (2.16
g, 22.45 mmol) were added. The vial was sealed, and the mixture was
stirred at 80 °C overnight. The salts were filtered off and rinsed
with methanol. The filtrate was concentrated. The crude product was
purified by preparative HPLC. Product containing samples were united,
the solvents were evaporated with a rotary evaporator and the residue
was lyophilized. 730 mg (100% purity, 60% yield) of the title compound
was obtained. LC–MS (Method 2): Rt = 1.61 min; MS (ESIpos): m/z = 386 [M + H]⁺. ¹H NMR (600 MHz, DMSO-d₆) δ [ppm]
= 10.28–11.41 (m, 1H), 8.26 (s, 1H), 7.77 (d, J = 8.1 Hz, 1H), 7.75 (br s, 1H), 7.47 (t, J = 7.9
Hz, 2H), 7.27 (t, J = 7.3 Hz, 1H), 6.61 (br s, 1H),
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Methyl-3-formylbenzoate is a chemical compound used in various laboratory applications. It is a colorless, crystalline solid that serves as a precursor or intermediate in organic synthesis. The core function of this product is to provide a source of the 3-formylbenzoate moiety for further chemical transformations and reactions. No additional details or interpretations about its intended use can be provided while maintaining an unbiased and factual approach.

3 phenylpropionaldehyde by Thermo Fisher Scientific

3-Phenylpropionaldehyde is a colorless liquid organic compound with the chemical formula C6H5CH2CH2CHO. It is a versatile intermediate used in the synthesis of various organic compounds.

What are the common uses of methyl carbamate?

Methyl carbamate is a versatile chemical compound with a variety of applications. It is commonly used as an insecticide, fungicide, and herbicide to protect crops and other plants from pests and diseases. Additionally, methyl carbamate is utilized in the production of other chemicals, such as pharmaceuticals and industrial solvents. It is a useful tool for researchers and industries that require effective pest and weed control solutions.

What are the potential health risks associated with methyl carbamate exposure?

Exposure to methyl carbamate can result in cholinergic effects, such as nausea, vomiting, diarrhea, and breathing difficulties. These symptoms occur due to the compound's ability to inhibit the enzyme acetylcholinesterase, which is responsible for the breakdown of the neurotransmitter acetylcholine. Proper precautions, such as the use of personal protective equipment, should be taken when handling methyl carbamate to minimize the risk of accidental exposure and potential health consequences.

Are there any variations or different types of methyl carbamate available?

While methyl carbamate is a specific chemical compound, there may be different formulations or product variations available depending on the intended use and application. For example, some methyl carbamate-based pesticides may contain additional inert ingredients or adjuvants to enhance their effectiveness or stability. Researchers studying methyl carbamate should carefully review the composition and specifications of any products they intend to use to ensure they are selecting the most appropriate option for their research needs.

How can PubCompare.ai assist researchers in optimizing their methyl carbamate studies?

PubCompare.ai's AI-powered protocol comparison tools can be invaluable for researchers studying methyl carbamate. The platform allows you to efficiently screen the existing literature, including publications, preprints, and patents, to identify the most reproducible and accurate methods for your work. PubCompare.ai's intelligent analysis can highlight key differences in protocol effectiveness, enabling you to choose the best option for your specific research goals and ensure the highest level of accuracy and reliability in your methyl carbamate studies. The platform's cutting-edge analytics can elevate your methyl carbamate research and help you achieve more meaningful and impactful results.

More about "Methyl carbamate"

Methyl carbamate, also known as carbamic acid methyl ester, is a versatile chemical compound with a wide range of applications.
It is a white, crystalline solid that is soluble in water and organic solvents, making it a useful ingredient in various industries.
One of the primary uses of methyl carbamate is as a pesticide, serving as an insecticide, fungicide, and herbicide.
Its ability to disrupt the nervous system of pests makes it an effective tool in protecting crops and plants.
Researchers studying methyl carbamate's pesticidal properties can utilize PubCompare.ai's AI-powered protocol comparison tools to locate relevant publications, preprints, and patents, and identify the most reproducible and accurate methods for their work.
In addition to its pesticidal applications, methyl carbamate is also used in the production of other chemicals, such as Formic acid, XBridge C18, Cathepsin B, Sunfire Prep-C18, N-Boc-2-aminoacetaldehyde, 4-Methoxybenzaldehyde, Imidazole-4-carboxaldehyde, and Methyl-3-formylbenzoate.
These compounds have a variety of uses in fields like pharmaceuticals, materials science, and organic synthesis.
Exposure to methyl carbamate can result in cholinergic effects, such as nausea, vomiting, diarrhea, and breathing difficulties.
Therefore, proper precautions should be taken when handling this substance.
Researchers studying methyl carbamate can utilize PubCompare.ai's cutting-edge analytic tools to compare and identify the most reproducible and accurate protocols for their experiments, ensuring the safety and efficacy of their work.
Whether you're working on pesticide development, chemical synthesis, or any other methyl carbamate-related research, PubCompare.ai's advanced tools can help you streamline your processes, improve your outcomes, and advance the field of study.
By leveraging the power of AI-driven protocol comparisons, you can elevate your methyl carbamate studies and make significant contributions to the scientific community.