5-CHLOROQUINOLINE

Yellow Solid

To a suspension of 5-aminoquinoline (756 mg, 5.24 mmol) in aqueous 2 N HCl (31 mL) cooled to 0 °C was added a solution of NaNOStep 1: Preparation of compound 181-2 [00624] m-CPBA (39 g, 192 mmol) was added to a solution of compound 181-1 (30 g, 183 mmol) in DCM (500 mL) and the mixture was stirred at 15 C for 12 h. Saturated aqueous Na2SO3 (aq, 1000 mL) was added, and the mixture was stirred at 15 C for another 0.5 hour. The reaction was checked by potassium iodide-starch test paper until the test paper did not change to blue. The mixture was extracted with DCM (500 mL*3).The combined organic phase was washed with brine (500 mL), dried over anhydrous Na2SO4 and then filtered. The filtrate was concentrated to give a residue. The residue was purified by silica gel chromatography (column height: 250 mm, diameter: 100 mm, 100-200 mesh silica gel, Petroleum ether/Ethyl acetate = 50/1~0/1) to provide compound 181-2 (19 g, 49%) as a yellow solid.General procedure: To solution of 5-methoxyquinoline 2a (104 mg, 0.66 mmol) in CH2Cl2 (3 mL) was added meta-chloroperoxybenzoic acid (195 mg, 1.13 mmol) at 0 C for 30 min. The mixture was allowed to warm to room temperature and stirred for additional 3 h. The reaction is queched with 4 N NaOH and extracted with CH2Cl2. The combined organic extracts were washed with brine, dried over anhydrous MgSO4 and concentrated under reduced pressure to give the crude N-oxide, which was directly used for the next step without purification. To solution of the resulting N-oxide in CH2Cl2 (2.5 mL) was adeed phosphorus oxychloride (0.09 mL, 0.99 mmol). The reaction mixture was refluxed at 60 C for 3 h, allowed to cool to room temperature and poured into ice-water. The resulting mixture was treated with 4 N aqueous NaOH until pH reached to around 10. The organic phase was extracted with CH2Cl2 (3 x 5 mL), washed with brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. The crude residue was purified by column chromatography on silica gel (EtOA/CH2Cl2/Hexane = 1:2:4) to give 5-methoxy-2chloroquinoline 4a (40.1 mg, 32%)General procedure: To a solution of the corresponding N-heterocycles (10.0 mmol) in CH2Cl2 (20 mL), m-chloroperoxybenzoic acid (m-CPBA, 20.0 mmol, 2.0 equiv) was added at 0 C. The reaction mixture was allowed to stir at room temperature for 12 h. Then saturated aqueous NaHCO3 (20 mL) was added. The aqueous was extracted with CH2Cl2 (10 mL x 3) and the combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel with EtOAc/n-hexene or EtOAc/MeOH to afford desired N-oxides.To a suspension of 5-aminoquinoline (756 mg, 5.24 mmol) in aqueous 2 N HCl (31 mL) cooled to 0 C was added a solution of NaNO2 (470 mg, 6.80 mmol) in H2O (14 mL). The reaction mixture was stirred at 0 C for 30 min and a solution of CuCl (644 mg, 6.51 mmol) in conc. HCl (16 mL) was added. The mixture was allowed to warm to room temperature and stirred for additional 24 h. Saturated NaHCO3 was slowly added to the mixture until no gas was generated. The organic phase was extracted with CH2Cl2 (3 x 50 mL), washed with brine, dried over anhydrous MgSO4, and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (EtOAc/hexane = 1:1) to give To a solution of 5-quinolinamine (9 g, 62.4mmo]) in water (80 mL) at 0 C was added concentrated NC] (5.2 mL, 62.4 mmol) and NaNO2 (6.5 g, 93.6 mmol) portionwise. Themixture was stirred at 0 C for 1 h, then a solution of CuCI (9.2 g, 93.7 mmol) in concentrated HC1 (5.2 mL, 62.4 mmol) was added dropwise at 0 C. After stirring at 0 C for 2 h, the mixture was made basic with sat. aq. NaHCO3 to pH 7 and then extracted with EtOAc (100 mL x 3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The cmde residue was purified by siLica gel chromatography(petroleum ether / EtOAc = 9: 1 to 5 : 1) to give the title compound (9.2 g, 90%) as clear oil.?H NMR (400 MHz, DMSO-d6) 8 8.99 - 8.98 (m, 111), 8.51 (d, J 8.0 Hz, IN), 8.01 (d, .J 8.0 Hz, 111), 7.77 - 7.73 (m, 211), 7.68 - 7.65 (m, IN).

Quinoline dyes and pharmaceutical intermediates.

Molecular Weight:163.60
XLogP3:3.3
Hydrogen Bond Acceptor Count:1
Exact Mass:163.0188769
Monoisotopic Mass:163.0188769
Topological Polar Surface Area:12.9
Heavy Atom Count:11
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes