The solid 6-bromo-quinolin-4-ol (52 g, 232.1 mmol) was added to phosphorus oxychloride (213.5 mL) and then the mixture was heated to reflux for 6 h to afford a light brown solution. 10558] The bicyclic compound 3-2 is prepared from bromoaniline 3-1 using diethyl 2-(ethoxymethylene)malonate or a similar reagent. Deprotection and removal of the carboxylic acid, followed by halogenation using a reagent such as phosphorus oxychloride yields compound 3-5. Derivatization with pyridine boronate in Suzuki coupling conditions yields 3-6, which is reacted in a second Suzuki reaction with a benzothiazolyl boronate to yield compound 3-7. Subsequent heating in hydrochloric acid in a solvent such as methanol results in removal of an acetyl group.4.1.8 6-Bromo-4-chloroquinoline. The solution of the compound from Example 17b (2 g, 8.9 mmol) in POCITo a suspension of 6-bromo-4-hydroxyquinolin (14.55 g, 64.9 mmol) in toluene (20mL) was added POCh (6.05 mL, 64.9 mmol) slowly. The reaction was stirred at 115°C for 4 h, then cooled down to 0°C and diluted with DCM (400 mL). The mixture was washed with 4MNaOH (70 mL) followed by brine (100 mL), dried over anhydrous Na2S04 and concentrated invacuo. The residue was recrystallized in n-heptane (150 mL) to give the title compound as ayellow solid (5.5 g, 32percent). The title compound was characterized by LC-MS and 1H NMR asshown below:LC-MS (ESI, pos. ion) m/z: 242 [M+Ht;1H NMR (400 MHz, CDCh) 8 (ppm): 7.50 (d, J= 4.72 Hz, 1H), 7.82 (dd, J= 8.96 Hz, 2.16 Hz, 1H), 7.98 (d, J= 8.92 Hz, 1H), 7.95 (d, J= 2.16 Hz, 1H), 8.34 (d, J= 4.68 Hz, 1H).To 6-bromo-4-hydroxyquinoline (14.55g, 64 . 9mmol) toluene (20 ml) is slowly added in solution POCl willL0g (44.63 mol) of 6-bromoquinolin-4 (1H) -one, 100 ml of toluene and 12.25 g (89.26 mol) of phosphorus trichloride were added to a 250 ml three-necked flask and heated to reflux for 2 hours. , Dried and dried. The solid was beaten with ether (100 ml), filtered and dried to give a yellow powder (yield 92.6percent).Diphenyl ether (80 ml) was added to 4-bromoaniline (4.5 g) and 5-(methoxymethylene)-2, 2-dimethyl-1, 3-dioxan-4, 6-dione (5.4 g), and the mixture was stirred at 80°C for one hr. Biphenyl (24.2 g) was added thereto, and the mixture was stirred at 220°C for 3 hr. The reaction mixture was cooled to room temperature, and diethyl ether was added to the cooled mixture. The precipitated crystal was collected by filtration and was washed with diethyl ether. The residue was purified by column chromatography with a hexane-acetone system to give 6-bromoquinolone (1.57 g, yield 27percent). Thionyl chloride (5 ml) and a minor amount of dimethylformamide were added to 6-bromoquinolone (1.6 g), and the mixture was stirred under reflux for 3 hr. The reaction mixture was added to a saturated aqueous sodium bicarbonate solution under ice cooling, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography with a hexane-ethyl acetate system to give 6-bromo-4-chloroquinoline (1.43 g, yield 85percent).A mixture of 4 (17.0 g, 131.5 mmol), POCl
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