8-Bromo-1-chloroisoquinoline

S4. Take another 2L four-necked flask with 10 ml of N, N-dimethylformamide and add 2.5 g of Step 3: To a stirred solution of 20 (0.5 g) in 1 , 4-dioxane (20 ml_) was added NH2NH2 (0.1 ml_) and the mixture was heated to 64 0C overnight. Additional 0.1 ml_ of NH2NH2 was added and stirring was continued for additional 5 h at 64 0C. Solvent was evaporated under vacuum and the residue was directly used in the next step without further purification.To a cold (0 0C), stirred solution of product from above in anhydrous CH2CI2 (6 ml_) was added Et3N (0.42 g) followed by trifluoroacetic anhydride (0.56 g) dropwise over 5 min via a syringe. After being stirred at 0 0C for 1 h and at RT for an additional 1 h, the reaction was quenched with H2O (20 ml_). The organic layer was separated and the aqueous layer was extracted with CH2CI2 (3 x 20 ml_). The combined organic layers were dried over Mg2SO4, filtered, and concentrated under vacuum to afford a solid which was used directly in the next step without further purification.To a stirred solution of the intermediate from above in 1 , 2-dichloroethane (5 ml_) was added POCI3 (0.5 ml_) and the mixture was heated at 84 0C overnight. The mixture was cooled to RT, poured into ice-water, and carefully neutralized with NH4OH solution. The resulting solution was extracted with CH2CI2 (3 x 20 ml_). The combined organic layers were dried over Mg2SO4, filtered, and concentrated under vacuum to leave a residue which was purified by column chromatography on silica (elution with 50:1 CH2CI2:Me0H) to afford 22 (0.31 g) as a light yellow solid. LCMS: M is 316 at 4.05 min.Step 2: A solution of /V-oxide 19 in POCI3 (35 ml_) was heated to 105 0C overnight, followed by heating at 120 0C for additional 20 h. The mixture was cooled to RT, poured into ice-water, and neutralized with NH4OH solution. The resulting solution was extracted with CH2CI2 (3 x 30 ml_). The combined organic layers were dried over Mg2SO4, filtered, and concentrated under vacuum to leave a residue which was further purified by column chromatography on silica gel (elution with 10:1 hexane:ethyl acetate) to afford 20 (1.3 g) as a light brown solid. LCMS: M + 2 is 244 at 4.45 min.S3, another 2L four-bottle, built-in 40ml of phosphorus oxychloride, and taking the S1-step product 8-bromoisoquinoline nitrogen oxide 9 grams, slowly added in batches to the four-mouth bottle, During the process of adding, keep the temperature at 40C. After adding all, increase the temperature to 100C.After 2 hours of reaction, the reaction mixture was poured into 400 g of crushed ice, and the precipitated solid was collected and suction filtered.The filter cake is dissolved in sufficient amount of methylene chloride and washed with 150 ml of a 10% by mass aqueous solution of sodium carbonate to neutrality.The organic phase was washed once with 80 ml of saturated saline and dried over anhydrous sodium sulfate.Dry to obtain crude product, and then use 100-200 mesh silica gel column chromatography to isolate S3-step product

Molecular Weight:242.50
XLogP3:3.8
Hydrogen Bond Acceptor Count:1
Exact Mass:240.92939
Monoisotopic Mass:240.92939
Topological Polar Surface Area:12.9
Heavy Atom Count:12
Complexity:165
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes