Abstract: Herein, we describe 39 novel quinolone compounds bearing a hydrophilic amine chain and varied substituted benzyloxy units. These compounds demonstrate broad-spectrum activities against acid-fast bacterium, Gram-pos. and -neg. bacteria, fungi, and leishmania parasite. Compound 30 maintained antitubercular activity against moxifloxacin-, isoniazid-, and rifampicin-resistant Mycobacterium tuberculosis, while 37 exhibited low micromolar activities (<1 μg/mL) against World Health Organization (WHO) critical pathogens: Cryptococcus neoformans, Acinetobacter baumannii, and Pseudomonas aeruginosa. Compounds in this study are metabolically robust, demonstrating % remnant of >98% after 30 min in the presence of human, rat, and mouse liver microsomes. Several compounds thus reported here are promising leads for the treatment of diseases caused by infectious agents.
2-Methoxy-5-nitrophenol (CAS: 636-93-1) can be used in the preparation of Bosutinib (SKI-606) (CAS: 380843-75-4). Bosutinib, a small molecule that inhibits BCR-ABL and src tyrosine kinases, is utilized for treating chronic myelogenous leukemia.
Application In Synthesis of [ 636-93-1 ]
* 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.
1-[3-(2-methoxy-5-nitro-phenoxy)propyl]pyrrolidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
44%
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 0 - 20℃; for 5h;
To a solution of commercially available 2-methoxy-5-nitro-phenol: 1-01 a (19.6 g, 0.12 mol) in THF (200 ml_), PPh3 (61 g, 0.23 mol), commercially available 3-pyrrolidin-1 -yl-propan-1 -ol : R-01 a (15 g, 0.16 mol) and DEAD (40 g. 0.23 mol) were added at 0 C, the solution was stirred at RT for 5 h. The reaction mixture was concentrated and extracted with AcOEt. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give the crude product which was purified by column chromatography (eluent gradient PE:EA=1 :0 to 3:1 ) to give intermediate I- 02a (14 g, 44% yield) as a yellow solid. ESI-MS (M+1 ): 281 calc. for
44%
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 0 - 20℃; for 5h;
To a solution of commercially available 2-methoxy-5-nitrophenol (1-01a, 19.6 g, 0.12 mol) in THF (200 mL), PPh3 (61 g, 0.23 mol), commercially available <strong>[19748-66-4]3-pyrrolidin-1-yl-propan-1-ol</strong> (R-01a, 15 g, 0.12 mol) and DEAD (40 g. 0.23 mol) were added at 0C, the solution was stirred at room temperature for 5 hours. The reaction mixture was concentrated and extracted with AcOEt. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give the crude product which was purified by column chromatography to give intermediate I-02a (14 g, 44%) as a yellow solid. ESI-MS (M+1): 281 calc. for C14H20N2O4: 280.1.
44%
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 0 - 20℃; for 5h;
To a solution of commercially available 2-methoxy-5-nitro-phenol: 1-01 a (19.6 g, 0.12 mol) in THF (200 mL), PPh3(61 g, 0.23 mol), commercially available 3-pyrrolidin-1 -yl-propan-1 - ol (R-01 a, 15 g, 0.16 mol) and DEAD (40 g, 0.23 mol) were added at 0 C and the solution was stirred at room temperature for 5 hours. The reaction mixture was concentrated and extracted with AcOEt. The combined organic layers were washed with brine, dried over anhydrous Na2S04, filtered and concentrated to give the crude product which was purified by column chromatography (Si02, Petroleum ether/Ethyl acetate = 1/0 to 3/1 ) to give intermediate -02a (14 g, 44%) as a yellow solid. ESI-MS (M+1 ): 281 calc. for Ci4H20N2O4: 280.1 .
With caesium carbonate; sodium iodide; In N,N-dimethyl-formamide; at 110℃; for 16h;
Into a 50-mL round-bottom flask, was placed 2-methoxy-5-nitrophenol (1.1 g, 6.50 mmol, 1.00 equiv.), <strong>[57616-74-7]4-<strong>[57616-74-7](3-chloropropyl)morpholine hydrochloride</strong></strong> (1.3 g, 6.50 mmol, 1.00 equiv.), Cs2C03 (6.39 g, 19.61 mmol, 3.00 equiv.), Nal (980 mg, 1.00 equiv.), N,N- dimethylformamide (10 mL). The resulting solution was stirred for 16 h at 110 C. The resulting solution was diluted with 50 mL of H20. The resulting solution was extracted with 100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 5x100 mL of brine. The resulting mixture was concentrated under vacuum. This resulted in 1.17 g (61%) of 4-[3-(2-methoxy-5-nitrophenoxy)propyl]morpholine as a yellow solid
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
