2,3-Dibromotoluene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Bromine (168 g., 1.05 mole) is added over about one hour, with vigorous stirring, to 117.5 g. (0.47 mole) of 2,3-dibromotoluene at 190° C. After the addition is complete, the mixture is cooled to 100° C., then 120 cc. of concentrated sulfuric acid is added and the mixture is stirred for one hour at 100° C. Temperature is raised to 140° C. for five minutes, then the mixture is cooled and the reaction is quenched in ice water. The solid is extracted into ether, and the ether extract is washed with water, then dilute aqueous sodium bicarbonate until the acid is completely removed, and filtered. Removing the ether by evaporation gives 2,3-dibromobenzaldehyde as the residue. at 190° C After the addition Temperature is raised to 140° C. for five minutes the mixture is cooled the reaction is quenched in ice water The solid is extracted into ether the ether extract is washed with water dilute aqueous sodium bicarbonate until the acid is completely removed filtered Removing the ether by evaporation

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Bromine (168 g., 1.05 mole) is added over about one hour, with vigorous stirring, to 117.5 g. (0.47 mole) of 2,3-dibromotoluene at 190° C. After the addition is complete, the mixture is cooled to 100° C., then 120 cc. of concentrated sulfuric acid is added and the mixture is stirred for one hour at 100° C. Temperature is raised to 140° C. for five minutes, then the mixture is cooled and the reaction is quenched in ice water. The solid is extracted into ether, and the ether extract is washed with water, then dilute aqueous sodium bicarbonate until the acid is completely removed, and filtered. Removing the ether by evaporation gives 2,3-dibromobenzaldehyde as the residue. at 190° C After the addition Temperature is raised to 140° C. for five minutes the mixture is cooled the reaction is quenched in ice water The solid is extracted into ether the ether extract is washed with water dilute aqueous sodium bicarbonate until the acid is completely removed filtered Removing the ether by evaporation

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A dry 250 mL 3-necked flask was charged with Pd2(dba)3 (266 mg, 2 mol %), BINAP, 384 mg, 4 mol %), and sodium t-butoxide (2.2 g, 0.023 mol) in 50 mL dry toluene. After 5 minutes, 23A cis-N,N′-bis(7-chloroquinolin-4-yl)cyclohexane-1,4-diamine (4.00 g, 0.0145 mol) was added in one portion followed by dibromotoluene (3.6 g, 0.0145 mol). The solution was heated at 70° C. under nitrogen overnight. The contents were filtered, concentrated and the residue was purified by flash chromatography (5% methanol in dichloromethane) to provide 1.03 g, a 16% yield. MS (ESI(+)Q1MS m/z 445 (M+2 H)+; 1 H NMR (300 MHz, MeOH) δ ppm 8.51 (d, 1 H), 8.37 (d, 1 H), 7.86 (d, 1 H), 7.69 (dd, 1 H), 6.96 (d, 1 H), 6.66 (s, 1 H), 6.61 (s, 1 H), 6.49 (s, 1 H), 3.98 (m, 1 H), 3.63 (m, 1 H), 2.22 (s, 3 H), 1.85-2.01 (m, 8 H). The contents were filtered concentrated the residue was purified by flash chromatography (5% methanol in dichloromethane) to provide 1.03 g

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of dibromotoluene (382 mg, 1.527 mmol, prepared using similar method described for Example 1) in DMF (2 mL) was added slowly to a mixture of compound 6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-ol (200 mg, 0.763 mmol) and Cs2CO3 (746 mg, 2.289 mmol) in DMF (10 mL) at 100° C. After 10 min, the mixture was concentrated in vacuo. The resulting residue was diluted with water (50 mL) and extracted with ethyl acetate (25 mL×3). The organic layer was washed with brine (50 mL), dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified using column chromatography (petroleum ether:ethyl acetate=50:1) to provide 2-chloro-11-fluoro-6-phenyl-6H-pyrido[2′,3′:5,6][1,3]oxazino[3,4-a]indole (187 mg, yield: 70.0%). 1H-NMR (CDCl3, 400 MHz) δ 7.43 (s, 1H), 7.23˜7.35 (m, 3H), 7.18 (s, 1H), 7.10 (s, 1H), 7.03˜7.08 (m, 4H), 6.79 (m, 1H), 6.65 (d, J=8.4 Hz, 1H). MS (M+H)+: 351/353. the mixture was concentrated in vacuo The resulting residue was diluted with water (50 mL) extracted with ethyl acetate (25 mL×3) The organic layer was washed with brine (50 mL) dried over Na2SO4 concentrated in vacuo The resulting residue was purified

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Bromine (168 g., 1.05 m.) is added over about one hour, with vigorous stirring, to 117.5 g. (0.47 m.) of 2,3-dibromotoluene at 190°C. After the addition is complete, the mixture is cooled to 100°C., then 120 cc. of concentrated sulfuric acid is added and the mixture is stirred for one hour at 100°C. Temperature is raised to 140°C. for 5 minutes, then the mixture is cooled and the reaction is quenched in ice water. The solid is extracted into ether, and the ether extract is washed with water, then dilute aqueous sodium bicarbonate until the acid is completely removed, and filtered. Removing the ether by evaporation gives 2,3-dibromobenzaldehyde as the residue. at 190°C After the addition Temperature is raised to 140°C. for 5 minutes the mixture is cooled the reaction is quenched in ice water The solid is extracted into ether the ether extract is washed with water dilute aqueous sodium bicarbonate until the acid is completely removed filtered Removing the ether by evaporation

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Bromine (168 g., 1.05 mole) is added over about 1 hour, with vigorous stirring, to 117.5 g. (0.47 mole) of 2,3-dibromotoluene at 190° C. After the addition is complete, the mixture is cooled to 100° C., then 120 cc. of concentrated sulfuric acid is added and the mixture is stirred for 1 hour at 100° C. Temperature is raised to 140° C. for five minutes, then the mixture is cooled and the reaction is quenched in ice water. The solid is extracted into ether, and the ether extract is washed with water, then dilute aqueous sodium bicarbonate until the acid is completely removed, and filtered. Removing the ether by evaporation gives 2,3-dibromobenzaldehyde as the residue. at 190° C After the addition Temperature is raised to 140° C. for five minutes the mixture is cooled the reaction is quenched in ice water The solid is extracted into ether the ether extract is washed with water dilute aqueous sodium bicarbonate until the acid is completely removed filtered Removing the ether by evaporation

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Bromine (168 g., 1.05 mole) is added over about one hour, with vigorous stirring, to 117.5 g. (0.47 mole) of 2,3-dibromotoluene at 190° C. After the addition is complete, the mixture is cooled to 100° C., then 120 cc. of concentrated sulfuric acid is added and the mixture is stirred for one hour at 100° C. Temperature is raised to 140° C. for five minutes, then the mixture is cooled and the reaction is quenched in ice water. The solid is extracted into ether, and the ether extract is washed with water, then dilute aqueous sodium bicarbonate until the acid is completely removed, and filtered. Removing the ether by evaporation gives 2,3-dibromobenzaldehyde as the residue. at 190° C After the addition Temperature is raised to 140° C. for five minutes the mixture is cooled the reaction is quenched in ice water The solid is extracted into ether the ether extract is washed with water dilute aqueous sodium bicarbonate until the acid is completely removed filtered Removing the ether by evaporation