2-bromo-1-(2,5-dichlorophenyl)ethanone

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

Procedure: This compound was prepared from 1-benzo[1,3]dioxol-4-yl-ethanone (2.15 g, 13.1 mmol) in the manner described for 2-bromo-1-(2,5-dichlorophenyl)ethanone (Method I-2), affording 1.54 g (48%) of 1-benzo[1,3]dioxol-4-yl-2-bromo-ethanone as an off-white solid.

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

Procedure: This compound was prepared from 1-benzo[1,3]dioxol-4-yl-ethanone (2.15 g, 13.1 mmol) in the manner described for 2-bromo-1-(2,5-dichlorophenyl)ethanone (Method I-2), affording 1.54 g (48%) of 1-benzo[1,3]dioxol-4-yl-2-bromo-ethanone as an off-white solid.

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

Procedure: This compound was prepared from 1-(2-bromo-4-fluoro-phenyl)-ethanone (2.5 g, 11.52 mmol) in the manner described for 2-bromo-1-(2,5-dichlorophenyl)-ethanone (Method I-2), affording 2.14 g (63%) of 2-bromo-1-(2-bromo-4-fluoro-phenyl)-ethanone as a clear oil. 1H-NMR (CD2Cl2) δ 7.57 (dd, J=9, 6 Hz, 1H), 7.44 (dd, J=8, 2 Hz, 1H), 7.21 ((m, 7.21–7.14, 1H), 4.51 (s, 2H); TLC Rf=0.38, 15% ethyl acetate-hexanes.

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

Procedure: This compound was prepared from 1-(2-bromo-phenyl)-ethanone (2.5 g, 12.6 mmol) in the manner described for 2-bromo-1-(2,5-dichlorophenyl)ethanone (Method I-2), affording 1.98 g (57%) of 2-bromo-1-(2-bromo-phenyl)-ethanone as a clear oil. 1H-NMR (CD2Cl2) δ 8.13 (t, J=2 Hz, 1H), 7.92 (dm, J=8 Hz, 1H), 7.78 (dm, J=8 Hz, 1H), 7.42 (t, J=8 Hz, 1H), 4.49 (s, 2H); TLC Rf=0.38, 15%, ethyl acetate-hexanes.

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

Procedure: This compound was prepared from 1-(2-bromo-phenyl)-ethanone (2.5 g, 12.6 mmol) in the manner described for 2-bromo-1-(2,5-dichlorophenyl)ethanone (Method I-2), affording 1.98 g (57%) of 2-bromo-1-(2-bromo-phenyl)-ethanone as a clear oil. 1H-NMR (CD2Cl2) δ 8.13 (t, J=2 Hz, 1H), 7.92 (dm, J=8 Hz, 1H), 7.78 (dm, J=8 Hz, 1H), 7.42 (t, J=8 Hz, 1H), 4.49 (s, 2H); TLC Rf=0.38, 15%, ethyl acetate-hexanes.

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

Procedure: This compound was prepared from 1-[2,4-bis(trifluoromethyl)phenyl]ethanone (5.0 g, 19.52 mmol) in the manner described for 2-bromo-1-(2,5-dichlorophenyl)ethanone, affording 4.12 g (63%) of a white solid. 1H-NMR (DMSO-d6) δ 8.28 to 8.16 (m, 3H), 4.98 (s, 2H);

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

Procedure: To 2,5-dichloroacetophenone (5.0 g, 26.45 mmol) in anhydrous tetrahydrofuran (53 mL) under argon was added phenyltrimethylammonium tribromide (9.94 g, 26.45 mmol, 1.0 eq) at 0° C. The reaction mixture was stirred at ambient temperature for 16 h, concentrated, and re-dissolved in ethyl acetate. The organic layer was washed with water (2×250 mL) and brine (1×150 mL), dried (MgSO4), filtered, and evaporated in vacuo. Purification using MPLC chromatography (Biotage) gave 3.47 g (52.5%) of 2-bromo-1-(2,5-dichlorophenyl)ethanone as a clear oil. 1H-NMR (DMSO-d6) δ 7.93 (dd, J=2.1 Hz, 0.9 Hz, 1H), 7.61 to 7.60 (m, 2H), 4.86 (s, 2H); concentrated re-dissolved in ethyl acetate The organic layer was washed with water (2×250 mL) and brine (1×150 mL) dried (MgSO4) filtered evaporated in vacuo Purification

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

Procedure: To 2,5-dichloroacetophenone (5.0 g, 26.45 mmol) in anhydrous tetrahydrofuran (53 mL) under argon was added phenyltrimethylammonium tribromide (9.94 g, 26.45 mmol, 1.0 eq) at 0° C. The reaction mixture was stirred at ambient temperature for 16 h, concentrated, and re-dissolved in ethyl acetate. The organic layer was washed with water (2×250 mL) and brine (1×150 mL), dried (MgSO4), filtered, and evaporated in vacuo. Purification using MPLC chromatography (Biotage) gave 3.47 g (52.5%) of 2-bromo-1-(2,5-dichlorophenyl)ethanone as a clear oil. 1H-NMR (DMSO-d6) δ 7.93 (dd, J=2.1 Hz, 0.9 Hz, 1H), 7.61 to 7.60 (m, 2H), 4.86 (s, 2H); concentrated re-dissolved in ethyl acetate The organic layer was washed with water (2×250 mL) and brine (1×150 mL) dried (MgSO4) filtered evaporated in vacuo Purification

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,5-Dichloroacetophenone (20.9 g, 0.11 mol) was dissolved in diethyl ether (300 mL) and the reaction mixture was cooled to 0° C. Bromine (5.66 mL, 0.11 mol) was added slowly dropwise and the reaction mixture was allowed to warm to room temperature over 20 minutes. The reaction mixture was treated with saturated aqueous NaHCO3 solution (250 mL). The organic layer was separated, dried over MgSO4 and concentrated in vacuo, yielding the title compound (20.0 g, 68%) as a yellow oil. δH (d6-DMSO) 7.94 (dd, J 2.2, 0.3 Hz, 1H), 7.61 (m, 2H), 4.88 (s, 2H). to warm to room temperature over 20 minutes The organic layer was separated dried over MgSO4 concentrated in vacuo

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

Procedure: The title compound was prepared in analogy to example 1 step e) from 89 mg (0.33 mmol) 2-bromo-1-(2,5-dichlorophenyl)ethanone and 79 mg (0.3 mmol) [3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-thiourea. The crude product was stirred with diethyl ether and little ethanol to yield 130 mg (100%) [4-(2,5-dichloro-phenyl)-thiazol-2-yl]-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine as a yellow solid. MS ISP (m/e): 431.2/433.0 (100/66) (M+H)+. 1H NMR (DMSO-D6, 250 MHz): δ (ppm)=10.80 (s, 1H), 9.29 (s, 1H), 8.15 (s, 1H), 8.08 (s, 1H), 7.69 (s, 1H), 7.67 (s, 1H), 7.61 (d, 1H), 7.51 (d, 1H), 7.45 (d, 1H), 7.15 (d, 1H), 3.93 (s, 3H), 2.34 (s, 3H).

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

Procedure: To an ice-cooled solution of 2-bromo-1-(2,5-dichlorophenyl)ethanone (0.10 g, 0.37 mmol) in N,N-dimethylformamide (8 mL) was added potassium phthalimide (76 mg, 0.41 mmol). The mixture was warmed to room temperature for 2 hours. The resultant mixture was then poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. Recrystallization with diethyl ether afforded 2-(2-(2,5-dichlorophenyl)-2-oxoethyl)isoindoline-1,3-dione as a white solid. (110 mg, 88% yield). 1H NMR (400 MHz, CDCl3): 7.92-7.94 (m, 2H), 7.78-7.80 (m, 2H), 7.72 (m, 1H), 7.45-7.46 (m, 2H), 5.08 (s, 2H). extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate filtered concentrated Recrystallization with diethyl ether

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

Procedure: To an ice-cooled solution of 2-bromo-1-(2,5-dichlorophenyl)ethanone (0.10 g, 0.37 mmol) in N,N-dimethylformamide (8 mL) was added potassium phthalimide (76 mg, 0.41 mmol). The mixture was warmed to room temperature for 2 hours. The resultant mixture was then poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. Recrystallization with diethyl ether afforded 2-(2-(2,5-dichlorophenyl)-2-oxoethyl)isoindoline-1,3-dione as a white solid. (110 mg, 88% yield). 1H NMR (400 MHz, CDCl3): 7.92-7.94 (m, 2H), 7.78-7.80 (m, 2H), 7.72 (m, 1H), 7.45-7.46 (m, 2H), 5.08 (s, 2H). extracted with ethyl acetate The organic layer was dried over anhydrous sodium sulfate filtered concentrated Recrystallization with diethyl ether