6-Bromo-2-chloroquinoxaline

Part C. Preparation of 6-bromo-2-chloroquinoxaline.; [001024] To a flask containing phosphorus oxychloride (3.4ml, 36.5mmol) was added the product fromPart B (255mg, l.lmmol) and the solution was heated at 6OCompound 39 (600 mg, 2.66 mmol) was added to cold phosphorous oxychloride (4 mL) in portions wise to give a slurry. To the resulting slurry was added drop wise N, N- dimethylaniline (0.4 ml, 2.93 mmol) below 15°C. The brick red mixture was refluxed for 15 min, and the resulting dark brown clear solution was then cooled to ambient temperature. It was added to ice cold water (40 mL) , and the mixture was basified slowly with 40percent aq. NaOH to pH 8. The solid was collected by filtration, washed with water (2x10 mL) and dried to give the title compound 40 (70percent) .6-bromoquinoxalin-2(1 H)-one (9.0 g, 40 mmol) was dissolved in POCI[001023] Part C. Preparation of 6-bromo-2-chloroquinoxaline.; [001024] To a flask containing phosphorus oxychloride (3.4ml, 36.5mmol) was added the product fromPart B (255mg, l.lmmol) and the solution was heated at 6O0C overnight. The solution was cooled to room temperature, poured over ice and the resulting solid collected by filtration to give the title compound (239mg, 87%).Compound 39 (600 mg, 2.66 mmol) was added to cold phosphorous oxychloride (4 mL) in portions wise to give a slurry. To the resulting slurry was added drop wise N, N- dimethylaniline (0.4 ml, 2.93 mmol) below 15C. The brick red mixture was refluxed for 15 min, and the resulting dark brown clear solution was then cooled to ambient temperature. It was added to ice cold water (40 mL) , and the mixture was basified slowly with 40% aq. NaOH to pH 8. The solid was collected by filtration, washed with water (2x10 mL) and dried to give the title compound 40 (70%) .6-bromoquinoxalin-2(1 H)-one (9.0 g, 40 mmol) was dissolved in POCI3 (50 mL) and DMF (2 mL) was added at RT. The mixture was heated at 50C for 2 hours. After completion of the reaction it was cooled to RT and was poured slowly into ice cold water. The mixture was stirred for 30 minutes and then filtered to afford crude product.The crude product was purified by column chromatography using neutral silica gel of 60- 120 mesh size. A gradient of 8-9 % DCM in hexane was used to elute the title compound (5.O g, 51%).1H NMR (d6-DMSO) D 9.03 (s, 1 H), 8.42 (d, 1H), 8.08 (dd, 1 H), 7.98 (d, 1H).To a stirred solution of the compound obtained from Preparation 29 (2 g, 8.89 mmol) in phosphorus oxychloride (15 mL), was added DMF (1 mL). The mixture was stirred at 120C for 1.5 hours then allowed to cool to room temperature. The dark solution was concentrated in vacuo and cautiously quenched with crushed ice. The aqueous suspension was neutralised with 10% potassium carbonate solution and extracted with DCM (2 x 30 mL). The combined organic phases were dried (Na2SO4), filtered and concentrated to give 1.94 g of the title compound as a brown solid.1H-NMR (400 MHz, DMSOd6): delta= 9.02(1 H, s), 8.40(1 H, d), 8.06(1 H, dd), 7.98(1 H, d). LCMS (run time = 2min): R4 = 1.69 min; m/z 243; 245 [M+H]+A slurry of 5-cyclopropyl-3-(2, 6-dichlorophenyl)-4-(7-azaspiro[3.5]non-1-en-2-yl)isoxazole (25 mg, 0.07 mmol, synthesis described in General Method A), Under nitrogen protection, Intermediate N1 (1 eq) was added to a three-neck flask equipped with a mechanical stirrer.Propylboronic acid (1eq), Potassium carbonate (5eq), Pd(Pph3)4(2%), Toluene 1000ml + ethanol 500ml + water 300ml, Stirring was turned on and heated to reflux for 8h.Organic phase silica gel column chromatography, concentrated, Recrystallization from toluene gave yellow powder N2 (9.0 g, 93.7%).Step 1: 6-Bromo-2-vinylquinoxaline A mixture of

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