Abstract: Heteroarenes bearing nitrogen centers such as pyridines and quinolines are ubiquitous in pharmaceuticals, agrochemicals, and other small molecules of medicinal interest. Among them, quinoline derivatives belong to a significant class of bioactive molecules in the field of drugs and pharmaceuticals and they also display significant activity against numerous viruses and bacterium. Previous studies on enantioselective synthesis of α-heterocyclic amine derivatives include diastereoselective addition of organometallics to enantiopure pyridyl imines derived from Ellman auxiliary, and enantioselective reduction of a pyridyl ketone, conversion to a leaving group, and azide displacement followed by the reduction to obtain the amine. In addition, numerous other methods have been developed to prepare alkylated N-heteroarenes. However, protocols for enantioselective synthesis are rather limited and these stereospecific transformations require stoichiometric amounts of optically pure reagents and do not create new stereogenic centers. Considering the aforementioned limitations, the Ge group investigated addition of a chiral Cu‒alkyl species, generated by insertion of alkenes into a chiral Cu‒H complex to quinoline N-oxides to produce chiral 2-alkylated quinolines. This strategy that utilizes quinoline N-oxide as an electrophile inspired us to expand the methodology to afford enantioenriched chiral 2-aminoalkyl quinolines from quinoline N-oxide and 2-azadienes via a copper-catalyzed process. However, there are possible challenges to this reaction including a reductive dimerization of 2-azadiene, v reduction of quinoline N-oxides to quinolines, and potential catalyst deactivation. If these challenges can be overcome, this strategy could represent a practical protocol to prepare chiral aminoalkylated quinolines from readily available quinoline N-oxides and alkenes.
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With N-Bromosuccinimide In dichloromethane at 20℃; for 12 h; Inert atmosphere
4.2 g of RL-0107 was placed in a 100 mL three-necked flask, and N-bromosuccinimide (NBS) was added thereto. Further, 60 mL of dichloromethane was added, and argon gasReplacement was done. The reaction was further carried out at room temperature for 12 hours. After completion of the reaction, sodium thiosulfate (Na2S 2 O 3) was added and extracted with a water / ethyl acetate system. The organic layer was collected, dried over anhydrous magnesium sulfateAfter drying, the solvent was removed and purified by column chromatography to obtain 5.9 g of RL-0106(Yield: about 93.1percent).
Reference：
[1] Chemical Communications, 2017, vol. 53, # 31, p. 4339 - 4341
[2] Patent: JP2018/118935, 2018, A, . Location in patent: Paragraph 0099; 0100
[3] Journal of the American Chemical Society, 2016, vol. 138, # 33, p. 10413 - 10416
2
[ 4964-76-5 ]
[ 959121-99-4 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 14, p. 2358 - 2363
(a) 7-(Methyloxy)quinoline; A suspension of NaH (3.3g; 137.93mmol) in anhydrous DMF (160ml) was cooled to 0°C with stirring under argon. 7-Quinolinol (8g; 55.17mmol) dissolved in anhydrous DMF (320ml) was added and the mixture was stirred at 0°C under argon for Ih. The mixture was then allowed to warm to rt and MeI (7.8ml; 55.17mmol) was added and the reaction was stirred for Ih. Ice water was then added cautiously and the resulting mixture extracted with EtOAc (3 x 500ml). The organic layer from this extraction was then washed with water (400ml) and brine (400ml). The resulting organic layer was dried with MgSO4 and solvents removed to afford the desired compound (8.76g; 99percent) MS (ES+) m/z 160 (MH+).
(b) 7-(Methyloxy)- 1 -(2-propen- 1 -yl)quinolinium iodide; 7-(Methyloxy)quinoline (8.76g;55.09mmol) and allyl iodide (19.72ml; 110.18mmol) were refluxed in toluene (120ml) at 950C for Ih, more allyl iodide (9.86ml;55.09mmol) was added and the temperature of the reaction increased to HO0C. After a further Ih the temperature of the reaction was increased to 1200C and reaction continued for a further 0.5h. The solvent was removed under vacuum and the resulting brown solid was washed with toluene and diethyl ether. The resultant solid were left to dry in a vacuum oven overnight to give the desired product (14.81g; 82percent) MS (ES+) m/z 201 (MH+).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
