1-(4-fluorophenyl)propan-2-one

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

Procedure: A mixture of 4-fluorophenyl acetone (50 grams) and 162.5 ml of N,N-dimethylformamide dimethyl acetal in 75 ml of acetonitrile is stirred for 12 hours and then the reaction mixture is concentrated on a rotary evaporator. The residual solid is suspended in 100 ml of hexane and filtered to give 59.6 grams of 1-(4-fluorophenyl)-2-(dimethylamino)ethenyl-2-propanone. the reaction mixture is concentrated on a rotary evaporator filtered

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

Procedure: 4-Fluorophenylacetone (388 μl, 2.9 mmol) in DCM (12 ml) was cooled to 0° C. and bromine (672 mg, 2.9 mmol) was slowly added. The mixture was stirred for 30 min and then concentrated in vacuo. The crude intermediate was added to a mixture of 6-chloro-1-(4-fluorophenyl)-1H-indazol-5-ol, (99c) (762 mg, 2.9 mmol) and potassium carbonate (804 mg, 5.8 mmol) in THF (12 ml). The mixture was stirred for 4 h, filtrated and concentrated. The crude product was purified by flash chromatography (EtOAc/heptane, product eluted at 40% EtOAc) to give the title compound (1.06 g, 88%). concentrated in vacuo The mixture was stirred for 4 h filtrated concentrated The crude product was purified by flash chromatography (EtOAc/heptane, product eluted at 40% EtOAc)

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

Procedure: 4-Fluorophenylacetone (388 μl, 2.9 mmol) in DCM (12 ml) was cooled to 0° C. and bromine (672 mg, 2.9 mmol) was slowly added. The mixture was stirred for 30 min and then concentrated in vacuo. The crude intermediate was added to a mixture of 6-chloro-1-(4-fluorophenyl)-1H-indazol-5-ol, (99c) (762 mg, 2.9 mmol) and potassium carbonate (804 mg, 5.8 mmol) in THF (12 ml). The mixture was stirred for 4 h, filtrated and concentrated. The crude product was purified by flash chromatography (EtOAc/heptane, product eluted at 40% EtOAc) to give the title compound (1.06 g, 88%). concentrated in vacuo The mixture was stirred for 4 h filtrated concentrated The crude product was purified by flash chromatography (EtOAc/heptane, product eluted at 40% EtOAc)

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

Procedure: The title compound is prepared from 4-fluorophenyl acetone via 2-fluoro-5-(2-oxo-propyl)-benzenesulfonyl chloride (Example 47a) following an identical sequence of reactions used for the synthesis of N-[5-(4-methoxy-3-sulfamoyl-phenyl)-4-methyl-thiazol-2-yl]-acetamide (Example 30) from 4-methoxyphenyl acetone.

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

Procedure: The title compound is prepared from 4-fluorophenyl acetone via 2-fluoro-5-(2-oxo-propyl)-benzenesulfonyl chloride (Example 47a) following an identical sequence of reactions used for the synthesis of N-[5-(4-methoxy-3-sulfamoyl-phenyl)-4-methyl-thiazol-2-yl]-acetamide (Example 30) from 4-methoxyphenyl acetone.

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

Procedure: To chlorosulfonic acid (25 ml, excess) cooled at −10° C. is added dropwise 4-fluorophenyl acetone (1.0 g, 6.57 mmol). The temperature is kept below 0° C. throughout the addition. The reaction mixture is then left to warm up to room temperature overnight. The reaction mixture is poured carefully onto ice (1500 ml). Once ice is melted, the aqueous layer is extracted with DCM (3×250 ml). The combined organic layers are dried over MgSO4, filtered and concentrated to afford the titled compound as an off-white solid. The temperature is kept below 0° C. throughout the addition The reaction mixture is then left The reaction mixture is poured carefully onto ice (1500 ml) the aqueous layer is extracted with DCM (3×250 ml) The combined organic layers are dried over MgSO4 filtered concentrated

Conditions: temp:-35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Treat a −35° C. solution of fuming nitric acid (32.3 mL, 723 mmol) with 4-fluorophenylacetone (1.756 ml, 13.14 mmol) and stir at −35° C. for 1 h. Pour the mixture onto ice, extract with DCM (2×), dry the combined organics over MgSO4, concentrate to dryness and purify via silica gel chromatography (EtOAc/Hex) to afford the title compound (1.07 g, 41%). 1H NMR (400 MHz, DMSO-d6): δ 7.97 (dd, J=7.4, 2.2 Hz, 1H), 7.58 (ddd, J=8.6, 4.6, 2.2 Hz, 1H), 7.52 (dd, J=11.3, 8.6 Hz, 1H), 3.95 (s, 2H), 2.17 (s, 3H). Pour the mixture onto ice extract with DCM (2×) dry the combined organics over MgSO4 concentrate to dryness purify via silica gel chromatography (EtOAc/Hex)

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

Procedure: To a stirred flask of chlorosulphonic acid (344 g, 2.96 mol) cooled to −10° C. is added dropwise 1-(4-fluoro-phenyl)-propan-2-one (10 g, 65 mmol). The reaction mixture is left stirring at room temperature overnight and then poured carefully onto ice. The resultant solution is extracted with ethyl acetate and the organic extracts combined, dried (MgSO4) and concentrated in vacuo to yield the titled compound. The reaction mixture is left poured carefully onto ice The resultant solution is extracted with ethyl acetate dried (MgSO4) concentrated in vacuo

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

Procedure: To a stirred flask of chlorosulphonic acid (344 g, 2.96 mol) cooled to −10° C. is added dropwise 1-(4-fluoro-phenyl)-propan-2-one (10 g, 65 mmol). The reaction mixture is left stirring at room temperature overnight and then poured carefully onto ice. The resultant solution is extracted with ethyl acetate and the organic extracts combined, dried (MgSO4) and concentrated in vacuo to yield the titled compound. The reaction mixture is left poured carefully onto ice The resultant solution is extracted with ethyl acetate dried (MgSO4) concentrated in vacuo

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

Procedure: A mixture of 4-fluorophenyl acetone (50 grams) and 162.5 ml of N,N-dimethylformamide dimethyl acetal in 75 ml of acetonitrile is stirred for 12 hours and then the reaction mixture is concentrated on a rotary evaporator. The residual solid is suspended in 100 ml of hexane and filtered to give 59.6 grams of 1-(4-fluorophenyl)-2-(dimethylamino)ethenyl-2-propanone. the reaction mixture is concentrated on a rotary evaporator filtered

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

Procedure: A mixture of 1-(4-fluorophenyl)-2-propanone (10.0 g) and N,N-dimethylformamide dimethylacetal (8.00 g) was stirred at 120° C. for 2 hrs. The reaction mixture was cooled, and hexane was added to the precipitated solids, which were collected by filtration to give 4-(dimethylamino)-3-(4-fluorophenyl)but-3-en-2-one (11.3 g, yield 83%) as a pale-yellow solid. The reaction mixture was cooled were collected by filtration

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

Procedure: 4-Fluorophenylacetone (388 μl, 2.9 mmol) in DCM (12 ml) was cooled to 0° C. and bromine (672 mg, 2.9 mmol) was slowly added. The mixture was stirred for 30 min and then concentrated in vacuo. The crude intermediate was added to a mixture of 6-chloro-1-(4-fluorophenyl)-1H-indazol-5-ol, (99c) (762 mg, 2.9 mmol) and potassium carbonate (804 mg, 5.8 mmol) in THF (12 ml). The mixture was stirred for 4 h, filtrated and concentrated. The crude product was purified by flash chromatography (EtOAc/heptane, product eluted at 40% EtOAc) to give the title compound (1.06 g, 88%). concentrated in vacuo The mixture was stirred for 4 h filtrated concentrated The crude product was purified by flash chromatography (EtOAc/heptane, product eluted at 40% EtOAc)