2-bromo-1-(2,4-dichlorophenyl)ethanone

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

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

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

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

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

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

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-(1,1,2,2-tetrafluoroethoxy)methyl-2,2-dimethyl-1,3-dioxolane (6.8 g), 2-bromo-1-(2,4-dichlorophenyl)ethanone (6 g.), sulphuric acid (0.3 ml at 96%) is heated at 120° C. for 3 hours, the acetone being formed in the reaction being distilled off. being distilled off

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

Procedure: A mixture of 13.5 parts of 2-bromo-1-(2,4-dichlorophenyl)ethanone, 5.5 parts of trimethoxymethane, 2 parts of 4-methylbenzenesulfonic acid and 80 parts of methanol is stirred and refluxed overnight (CaCl2 -tube). The reaction mixture is cooled and stirred for 30 minutes with 15 parts of a sodium hydroxide solution 50%. Then there are added 140 parts of 1,1'-oxybisethane and the mixture is washed with 300 parts of water. The organic phase is stirred with silica gel. The latter is filtered off and the filtrate is evaporated. The residue is dissolved in petroleumether. The solution is dried, filtered and evaporated, yielding 14.5 parts (92%) of 1-(2-bromo-1,1-dimethoxyethyl)-2,4-dichlorobenzene as a residue. The reaction mixture is cooled the mixture is washed with 300 parts of water The organic phase is stirred with silica gel The latter is filtered off the filtrate is evaporated The residue is dissolved in petroleumether The solution is dried filtered evaporated

Conditions: temp:130.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the solution of furan-2-carboxamide (56 mg, 0.5 mmol. 1 eq) and DIEA (0.13 mL, 0.75 mmo, 1.5 eq) in NMP (1 mL) was added 2-bromo-1-(2,4-dichlorophenyl)ethanone (0.6 mmol, 1.2 eq). Reaction mixture was heated at 130° C. for 15 h. The mixture was cooled down, diluted with 1 M HCl (30 mL) and extracted with EtOAc (40 mL). The organic layer was washed with 1 M HCl (30 mL), 5% solution of NaHCO3 (30 mL), brine (2×40 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The resulting residue was purified by HPLC purification to provide desired 4-(2,4-Dichloro-phenyl)-2-furan-2-yl-oxazole in a yield of 55% and HPLC 99.9% purity. LC-MS [M+H]-280.4 (C13H7Cl2NO2+H, requires 281.11). 1H NMR (DMSO-d6) δ 8.84 (s, 1H), 8.13 (d, 1H, J=8.5), 8.01 (s, 1H), 7.78 (s, 1H), 7.58 (d, 1H, J=8.5), 7.29 (d, 1H, J=3.5), 6.77 (m, 1H). Reaction mixture The mixture was cooled down extracted with EtOAc (40 mL) The organic layer was washed with 1 M HCl (30 mL), 5% solution of NaHCO3 (30 mL), brine (2×40 mL) dried over anhydrous Na2SO4 concentrated in vacuo The resulting residue was purified by HPLC purification

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 90 mg (0.33 mmol) 2-bromo-2′,4′-dichloroacetophenon and 79 mg (0.3 mmol) [3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-thiourea. The crude reaction was diluted with diethyl ether and the precipitate was filtered off and dried to yield 128 mg (99%) [4-(2,4-dichloro-phenyl)-thiazol-2-yl]-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine as a light yellow solid. MS ISP (m/e): 431.1/433.2 (100/65) (M+H)+. 1H NMR (DMSO-D6, 250 MHz): δ (ppm)=10.78 (s, 1H), 9.28 (s, 1H), 7.99 (s, 1H), 7.97 (d, 1H), 7.74 (s, 1H), 7.67 (s, 1H), 7.55 (d, 1H), 7.53 (s, 1H), 7.50 (d, 1H), 7.25 (d, 1H), 3.88 (s, 3H), 2.34 (s, 3H). The crude reaction the precipitate was filtered off dried

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 90 mg (0.33 mmol) 2-bromo-2′,4′-dichloroacetophenon and 79 mg (0.3 mmol) [3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-thiourea. The crude reaction was diluted with diethyl ether and the precipitate was filtered off and dried to yield 128 mg (99%) [4-(2,4-dichloro-phenyl)-thiazol-2-yl]-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine as a light yellow solid. MS ISP (m/e): 431.1/433.2 (100/65) (M+H)+. 1H NMR (DMSO-D6, 250 MHz): δ (ppm)=10.78 (s, 1H), 9.28 (s, 1H), 7.99 (s, 1H), 7.97 (d, 1H), 7.74 (s, 1H), 7.67 (s, 1H), 7.55 (d, 1H), 7.53 (s, 1H), 7.50 (d, 1H), 7.25 (d, 1H), 3.88 (s, 3H), 2.34 (s, 3H). The crude reaction the precipitate was filtered off dried

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

Procedure: 5 g (23.6 mmol) of diethyl 1H-pyrazole-3,5-dicarboxylate were dissolved in 100 ml of acetone, and 6.3 g (23.6 mmol) of 2-bromo-2,4-dichloroacetophenone and 3.6 g (26 mmol) of potassium carbonate were added. The mixture was stirred at RT for 12 h. The reaction mixture was concentrated and the residue was taken up in water and dichloromethane. The organic phase was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and concentrated on a rotary evaporator. The residue was triturated with diethyl ether, and the solid was filtered off with suction. This gave 9.48 g (94% of theory) of the product as a solid. The reaction mixture was concentrated The organic phase was washed with saturated aqueous sodium chloride solution dried over magnesium sulfate concentrated on a rotary evaporator The residue was triturated with diethyl ether the solid was filtered off with suction