7-Bromo-2-chloroquinoxaline

To the suspension of 7-bromoquinoxalin-2-ol (2 g, 8.88 mmol) in neat phosphorus oxychloride (7 mL) was added DMF (2drops). The mixture was heated to 100°C for 3h. Then it was cooled to room temperature. Phosphorus oxychloride was removed under vacuum, and the residue was dissolved into EtOAc and dropped into ice water with stirring. The mixture was extracted with EtOAc for three times, the combined organic layer was washed with saturated NaHCO3 solution. Then the organic layer was concentrated to afford 7-bromo-2-chloroquinoxaline as a solid in 93percent yield (2 g).To the suspension of 7-bromoquinoxalin-2-ol (2 g, 8.88 mmol) in neat phosphorus oxychloride (7 mL) was added DMF (2 drops). The mixture was heated to 100° C. for 3 h. Then it was cooled to room temperature. Phosphorus oxychloride was removed under vacuum, and the residue was dissolved into EtOAc and dropped into ice water with stirring. The mixture was extracted with EtOAc for three times, the combined organic layer was washed with saturated NaHCOPOClA suspension of 7-bromo-2(1 H)-quinoxalinone (prepared- by the method of Linda, P; Marino, G. Ric. Sci. Rend, Ser. A. 1963, 3, 225-228) (24.0 g; 107 mmol) in phosphorus oxychloride (40.0 mL) was stirred and heated under reflux for 2 h. The stirred mixture was allowed to cool then carefully poured into ice-water. The suspension was then filtered and the precipitate washed with water to afford the title compound (25.0 g; 96percent) as a beige solid. 7-bromo-2(1 H)-quinoxalinone (47.2g; 21 Ommol) was added to phosphorus oxychloride (470ml_).The reaction mixture was stirred at 100°C for 2 hours, cooled down to room temperature and evaporated to dryness. The crude product was taken up into DCM and poured onto ice, water and K7-bromo-2(1 H)-quinoxalinone (47.2g; 210mmol) was added to phosphorus oxychloride (470ml_).The reaction mixture was stirred at 100°C for 2 hours, cooled down to room temperature and evaporated to dryness. The crude product was taken up into DCM and poured onto ice, water and KA solution of 7-bromo-2(1 H)-quinoxalinone(prepared by the method of Linda, P; Marino, G. Ric. Sci., Rend. Sez. A. [2] 1963, 3, 225-228) (0.900 g, 4.00 mmol) was treated with phosphorus oxychloride (5.0 ml_). After heating to reflux overnight, the reaction mixture was poured into ice water, extracted thrice with ethyl acetate, dried over 7-Bromo-2-chloroquinoxaline. A solution of 7-bromo-2(1 H)-quinoxalinone (prepared by the method of Linda, P; Marino, G. Ric. Sci., Rend. Sez. A. [2] 1963, 3, 225-228) (0.900 g, 4.00 mmol) was treated with phosphorus oxychloride (5.0 ml_). After heating to reflux overnight, the reaction mixture was poured into ice water, extracted thrice with ethyl acetate, dried over magnesium sulfate, filtered, and concentrated in vacuo to give the title compound as an off-white solid (0.905 g, 93percent). 1 H NMR (400 MHz, DMSO-dStep C: Preparation of 2-chloro-7-bromo- uinoxaline300 mL POCI[0289] To a suspension of 7-bromoquinoxalin-2(lH)-one (224 g, 1 mol, 1.0 eq.) in POClTo a suspension of 7-bromoquinoxalin-2(1H)-one (224 g, 1 mol, 1.0 eq.) in POCl[0187] To a suspension of 7-bromoquinoxalin-2(lH)-one (224 g, 1 mol, 1.0 eq.) in POCl[0175] To a suspension of 7-bromoquinoxalin-2(lH)-one (224 g, 1 mol, 1.0 eq.) in POCIA stirred solution of 7-bromoquinoxalin-2(1 H)-one (1-71) (50 g, 222.1 mmol) in POCI3 (500 mL) was stirred and heated to reflux for 1 hr. The substrates took approximately 30 min to solubilize, and a further 30 min for the reaction to reach completion. The reaction was allowed to cool, and the excess POCI3 removed under vacuum. The reaction residue was poured onto crushed ice, and neutralized with solid NaHC03. The aqueous was extracted with EtOAc (3 x 250 mL). The organics were dried over Na2S04, filtered, and concentrated to afford a yellowish solid, which was washed with 5percent ether in hexanes to afford 7-bromo-2-chloroquinoxaline (I-72) (40 g, 70percent) as a brownish solid. LCMS (APCI), m/z 242.1 [M + H]+; 1H NMR (400 MHz, DMSO-c/6J 8 ppm 9.04 (s, 1 H), 8.33 (d, J = 2.0 Hz, 1 H), 8.03 - 8.1 1 (m, 2 H).b) 7-Bromo-2-chloroquinoxaline; A slurry of 7-bromo-2(1H)-quinoxalinone (22.2 mmol) in neat phosphorus oxychloride (50 ml) was heated at 120° C. for 20 hours. The reaction was cooled to ambient temperature then concentrated under reduced pressure to a purple residue. The residue was taken into ethyl acetate then slowly poured into ice-cold, saturated aqueous sodium bicarbonate solution (100 ml) and extracted with ethyl acetate. The extracts were washed with saturated aqueous sodium bicarbonate and brine then dried over anhydrous sodium sulfate and decolorizing charcoal. The slurry was filtered through Celite then concentrated under reduced pressure to give the title compound (3.0 g, 55percent) as a white solid. MS (ES)+ m/e 242.9; 244.8 [M+]Heat 1, 2-diaminobenzene (7.5 g, 69 mmol) and oxoacetic acid ethyl ester (20 mL) in ethanol (100 mL) at 120 °C for 18 h. Cool the mixture and filter the resulting crystals. Wash the crystals with ether and dry. Dissolve the crystals in acetic acid (300 mL), add bromine (5 mL), and stir for 1 h. Filter the resulting crystals, wash with ether, and reflux in POC13 (30 mL) for 18 h. Remove the solvent in vacuo, dilute with 3: 1 chloroform/isopropyl alcohol, and wash with the resulting solution with saturated sodium bicarbonate solution. Dry the organic layer (sodium sulfate), filter, concentrate in vacuo, and purify the residue by silica gel chromatography (dichloromethane to 10percent methanol/90percent dichloromethane) to afford 4.5 g (58percent) of the titled compound as a yellow solid. MS ES+ m/e 245 (M+1).

Molecular Weight:243.49
XLogP3:2.9
Hydrogen Bond Acceptor Count:2
Exact Mass:241.92464
Monoisotopic Mass:241.92464
Topological Polar Surface Area:25.8
Heavy Atom Count:12
Complexity:167
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes