Selective One-Pot<i>N</i>-Monomethylation of 2-Nitroanilines Under Ptc Conditions

Voskresensky, S.; Mąkosza, Mieczysław

doi:10.1080/00397910008087265

Cited by 7 publications

(5 citation statements)

References 8 publications

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“…The compounds were pure enough to be used for the next step without further purification. 5-( 6)Terbutyl-1H-benzimidazol-2-amine (45). BrCN (3.37 mmol) was added to a solution of commercially available 4-tertbutyl-1,2-phenylendiamine 58 (3.04 mmol) in a 1:1 mixture of H 2 O and MeOH (50 mL), and the mixture was heated at 60 • C for 5 h. About half of the solvent was eliminated under vacuum, and the mixture was extracted with EtOAc (50 mL × 5).…”

Section: Chemistry General Methodsmentioning

confidence: 99%

“…mp = 128-130 5-Chloro-N1-methylbenzene-1,2-diamine (83). 5-Chloro-2-nitro-N-methylaniline 82 [45] (2.68 mmol) was dissolved in boiling ethanol (50 mL), then Raney nickel (2400 slurry in H 2 O, 2 mL) was added, and the mixture was hydrogenated in a Parr apparatus at 15 psi for 2 h. The catalyst was filtered off, and the solvent was evaporated to give an oily residue that was used for the next step. Yield 85%.…”

Section: Chemistry General Methodsmentioning

confidence: 99%

“…The regioisomers were not separated but used as such in the next step. The N-methylbenzimidazole derivative 32 was synthesized as reported in Scheme 5, starting from 5-chloro-2-nitro-N-methylaniline 82 [45], which was catalytically reduced to give the corresponding amino derivative 83. Cyclization of the latter with cyanogen bromide afforded the benzimidazol-2-amino derivative 84, which was coupled with pyrazol-…”

Section: Chemistrymentioning

confidence: 99%

See 2 more Smart Citations

Structural Investigations on 2-Amidobenzimidazole Derivatives as New Inhibitors of Protein Kinase CK1 Delta

Calenda,

Catarzi,

Varano

et al. 2024

Pharmaceuticals

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Protein kinase CK1δ (CK1δ) is a serine-threonine/kinase that modulates different physiological processes, including the cell cycle, DNA repair, and apoptosis. CK1δ overexpression, and the consequent hyperphosphorylation of specific proteins, can lead to sleep disorders, cancer, and neurodegenerative diseases. CK1δ inhibitors showed anticancer properties as well as neuroprotective effects in cellular and animal models of Parkinson’s and Alzheimer’s diseases and amyotrophic lateral sclerosis. To obtain new ATP-competitive CK1δ inhibitors, three sets of benzimidazole-2-amino derivatives were synthesized (1–32), bearing different substituents on the fused benzo ring (R) and diverse pyrazole-containing acyl moieties on the 2-amino group. The best-performing derivatives were those featuring the (1H-pyrazol-3-yl)-acetyl moiety on the benzimidazol-2-amino scaffold (13–32), which showed CK1δ inhibitor activity in the low micromolar range. Among the R substituents, 5-cyano was the most advantageous, leading to a compound endowed with nanomolar potency (23, IC50 = 98.6 nM). Molecular docking and dynamics studies were performed to point out the inhibitor–kinase interactions.

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Section: Chemistry General Methodsmentioning

confidence: 99%

Section: Chemistry General Methodsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

See 1 more Smart Citation

Structural Investigations on 2-Amidobenzimidazole Derivatives as New Inhibitors of Protein Kinase CK1 Delta

Calenda,

Catarzi,

Varano

et al. 2024

Pharmaceuticals

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“…Methylation of phenols is an important transformation that regularly employs toxic and hazardous reagents such as methyl iodide or dimethyl sulfate . Dimethyl carbonate (DMC) as a methylating reagent for phenols and NH-containing heteroaromatic compounds has recently been reported with 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) under conventional thermal heating with long reaction times.…”

Section: Introductionmentioning

confidence: 99%

A Continuous Base-Catalyzed Methylation of Phenols with Dimethyl Carbonate

Tilstam¹

2012

Org. Process Res. Dev.

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We have found that the use of a conventional, heated, standard 316 stainless steel or steel-braided PTFE tube reactor is a good and easily scalable alternative to the use of continuous microwave-heated reactors. The heat-up is almost as fast as with microwave heating, and the reactors can easily be scaled towards large-scale production. The transfer of the reported microwave procedure to the continuous flow method went very smoothly, and we found that we could further optimize the reaction to a catalytic procedure where only 10 mol % of DBU is needed with only 3 equiv of DMC. The reaction can be run neat in cases where the starting material is soluble in DMC as phenol is, or with a small amount of DMF (2–3 vol). The reaction is efficient for different types of phenols, giving a clean reaction in high yields.

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“…Methylation is an important transformation that regularly employs toxic and hazardous reagents such as methyl iodide or dimethyl sulfate . The use of alternative reagents has been scarce due to the harsh conditions required with dimethylcarbonate or methanol as methylating agents.…”

Section: Introductionmentioning

confidence: 99%

A Continuous Methylation of Phenols and N,H-Heteroaromatic Compounds with Dimethyl Carbonate

Tilstam¹

2012

Org. Process Res. Dev.

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The methylation of phenolic substrates has been reevaluated using sulfolane as solvent instead of DMF. The change of solvent gave in all cases cleaner production of the anisole products in very good yields. The reaction requires 0.1 equiv of DBU, 2–3 equiv of DMC, and 2–5 vols of sulfolane depending on the substrate. At 220 °C the reaction time is 10 min. Sulfolane is completely stable under the reaction conditions, excluding unwanted impurities from the solvent. The reaction could also be extended to NH-indole and NH-imidazole derivatives utilizing 0.1 equiv of DBU and 2–3 equiv of DMC in 2 vols of sulfolane. All NH-heteroaromatic compounds gave clean N-methylation.

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Selective One-PotN-Monomethylation of 2-Nitroanilines Under Ptc Conditions

Cited by 7 publications

References 8 publications

Structural Investigations on 2-Amidobenzimidazole Derivatives as New Inhibitors of Protein Kinase CK1 Delta

Structural Investigations on 2-Amidobenzimidazole Derivatives as New Inhibitors of Protein Kinase CK1 Delta

A Continuous Base-Catalyzed Methylation of Phenols with Dimethyl Carbonate

A Continuous Methylation of Phenols and N,H-Heteroaromatic Compounds with Dimethyl Carbonate

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