6-Bromo-4-chloro-3-nitroquinoline

10556] The above reaction scheme illustrates the synthesis of a compound of the invention 2-13. Methylation of starting material 2-1 yields compound 2-2, which is subsequently reduced to the amine 2-3. In a separate reaction, compound 2-4 is converted to a salt, such as an HC1 salt, which is then reacted, for example, with 2-nitrovinyl-hydroxylamine to yield compound 2-6. Further cyclization yields compound 2-7. Halogenation with a reagent such as POd3 results in compound 2-8, which can be coupled with intermediate 2-3 to yield 2-9. The nitro moiety of 2-9 is subsequently reduced to an amine, and a further reaction with 4-nitrophenyl carbonochloridate results in the heterocycle 2-11. The desired compound 2-13 is then prepared by coupling to the benzoxazolyl boronate 2-12, for example in a Suzuki coupling.6-Bromo-3-nitroquinolin-4-ol (50 g) and N, N-diisopropylethylamine (60 mL) were added to acetonitrile (500 mL) and stirred for 10 to 15 min under nitrogen atmosphere. The reaction mass was cooled to a temperature of about 0-5 °C and phosphorusoxychloride (50 mL) was added dropwise to the cooled solution while maintaining the temperature below 10°C. The reaction mass was heated to 70 to 75 °C for 2 to 3 h. After completion of the reaction, the mass was cooled to 25 to 30°C. The cooled reaction mass was added dropwise into a mixture of ice-water (1.25 Kg) and sodium chloride (50 g) maintaining the temperature below 0°C. The mixture was stirred for 15 to 30 min. The compound obtained was filtered and washed with ice-cold water (250 mL). The wet compound was dissolved in MDC (750 mL) and filtered through celite bed. The bed was washed with MDC (250 mL). The combined organic layer from the filtrate was separated and washed with ice cold water (500 mL). The separated organic layer was dried over anhydrous sodium sulphate and subjected to distillation below 35°C under vacuum to obtain the title compound (55 g). This compound was dissolved in 500 mL of acetic acid and used for the next step without isolation. Yield: 93.5percentTo a solution of 7 (15 g, 0.056 mol) in acetonitrile (80 mL) and DIPEA (15.9 g, 0.123 mol), was added POCICompound 4a (19.5 g, 0.072 mol)Add to a three-necked flask containing phosphorus oxychloride (212 ml, 2.174 mol).Add 6 drops of DMF, Warm up to 110 ° C, Reflux for 0.2-3h.TLC detection [V (petroleum ether): V (ethyl acetate) = 1 : 1]Shows that the reaction is complete, The reaction liquid is distilled under reduced pressure to obtain a yellowish viscous material.Add ice saturated sodium bicarbonate solution (500 ml), Stir for 1h, Filtering, The filter residue was washed with water (20 mL).Extracted three times with ethyl acetate (30 mL×3).The extract was Concentrate the extract to dry riceyellowSolid 19.0g, The yield is 91.1percentAfter a suspension of 3g (10 mmol) in phosphorus oxychloride (15 mL) was added triethylamine slowly. The mixture was stirred and refluxed for 1.5 h. The phosphorus oxychloride was quenched with water carefully, then the suspension was filtered and the decolorized solid was recrystallized with ethyl acetate and petroleum ether. Yield 68percent. HPLC purity: 98.8percent.[0074] 26.8 g (99 mmol) of Intermediate 2 was placed in a 500-ml single-necked flask, added with 200 ml of phosphorusoxychloride, and refluxed at 120°C for 1 h. The reaction was monitored by TLC. After the reaction was completed, thereaction mixture was poured into a large amount of ice water and stirred, leading to formation of precipitates. The reactionmixture was filtered, and the filter cake was washed with ice water, and then dissolved in methylene chloride. The organicphase was washed with brine three times, dried by anhydrous magnesium sulfate, and rotary evaporated to dryness toafford 16.1 g of Intermediate 3. Yield: 53percent.26.8 g (99 mmol) of Intermediate 2 was placed in a 500 ml single-neck flask, 200 ml of phosphorus oxychloride was added thereto, 120 ° C under the return of lh, TLC monitoring. After completion of the reaction, it was poured into a large amount of ice water and stirred to precipitate. The filter cake was washed with ice water and dissolved in methylene chloride. The organic phase was washed three times with brine, dried over anhydrous magnesium sulphate, and dried to give intermediate 3 16.1 g, 53percent6-Bromo-3-nitroquinolin-4-ol (Compound of step 2, 20 g, 74.3 mmol) and POCIStep 3:

Molecular Weight:287.50
XLogP3:3.3
Hydrogen Bond Acceptor Count:3
Exact Mass:285.91447
Monoisotopic Mass:285.91447
Topological Polar Surface Area:58.7
Heavy Atom Count:15
Complexity:261
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes