7-BROMO-2-CHLORO-3-METHYLQUINOLINE

General procedure: To a stirred solution of 7-bromo-3-chloro-5-fluoroquinoline l-oxide (542 mg, 1.960 mmol) in CHCh (10 ml) was added POCI3 (1.867 ml, 20.03 mmol) at 25C. The resulting mixture was stirred at 65C for 2h under N2 atmosphere. The reaction mixture was poured onto ice cold water (50ml), carefully basified with solid NaHCCL and extracted the product with dichloromethane (50ml). Layers were separated, organic layer was washed with brine (50ml) and was dried over anhydrous NaiSCL. The organic layer was filtered and concentrated in vacuo to give l .2g of crude compound. This residue was purified by combiflash (Rf200, Teledyne/Isco) instrument onto a redisep Rf column with gradient elution (0 to 10%) of ethyl acetate in petroleum ether to afford the title compound (4l0mg, 70.9%) as a white solid. NMR (400 MHz, Chloroform-;/) d 8.49 - 8.43 (m, 1H), 8.04 (dt, J= 1.9, 1.0 Hz, 1H), 7.45 (dd, J= 8.9, l .7 Hz, 1H); LCMS m/z= 296.19 (M+l; 100%).a). Preparation of intermediate 41; Methanol sodium salt (41 ml) was added dropwise to a solution of 7-bromo-2-chloro-3- methylquinoline (39 mmol) in MeOH (100 ml). The mixture was stirred at 800C for 6 hours. Then the mixture was poured into ice and H2O and DCM was added. This mixture was extracted with DCM. The organic layer was dried (MgSO4), filtered, and the solvent was evaporated, yielding 18.4g of intermediate 41.Example A3 a) Preparation of intermediate 11 A mixture of 6-bromo-2-chloro-3-methyl-quinoline (0.0697 mol) and NaOCH3 30% (0.3483 mol) in methanol (90mol) was stirred and refluxed for 15 hours. The mixture was cooled, poured out into ice water and extracted with DCM. The organic layer was separated, dried (MgS04), filtered and the solvent was evaporated till dryness. The product was used without further purification, yielding 12.2g (69%) of intermediate 11.

Molecular Weight:256.52
XLogP3:4.2
Hydrogen Bond Acceptor Count:1
Exact Mass:254.94504
Monoisotopic Mass:254.94504
Topological Polar Surface Area:12.9
Heavy Atom Count:13
Complexity:188
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes