1-(3-BroMo-4-fluorophenyl)ethanol

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

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

Procedure: To a solution of EXAMPLE 412A (1.5 g, 6.8 mmol) and triphenyl phosphine (1.9 g, 7.2 mmol) in dimethylformamide (20 ml) was added bromine (1.1 g, 6.8 mmol) through a syringe. After the addition, the reaction mixture was stirred at room temperature for additional 15 minutes, and partitioned between water (100 ml) and ethyl acetate (200 ml). The organic phase was washed with brine and concentrated. The residue was purified by flash chromatography (2.6% ethyl acetate in hexane) to provide the title compound. MS (DCI/NH4) m/z 282 (M+H)+. After the addition partitioned between water (100 ml) and ethyl acetate (200 ml) The organic phase was washed with brine concentrated The residue was purified by flash chromatography (2.6% ethyl acetate in hexane)

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

Procedure: Synthesized from methyl 1-(5-bromopyrimidin-2-yl)-3-(methylthio)-1H-indole-6-carboxylate (1.0 g, 2.65 mmol) and 1-(3-bromo-4-fluorophenyl)ethanol (0.87 g, 3.98 mmol) analogously to the experimental procedure 289a). Yellow solid. Yield: 1.0 g (89% of theory)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 84A (9.8 g, 45 mmol) in trifluoroacetic acid (20 mL) was added triethylsilane (14.3 mL, 90 mmol). After stirring at 50° C. for 6 h, the reaction was quenched with 100 mL of saturated NaHCO3 solution and extracted with diethyl ether (3×). The combined organic layers were washed with brine, dried over MgSO4, and concentrated. The resulting residue was distilled at 200° C. to give 84B (85% purity). the reaction was quenched with 100 mL of saturated NaHCO3 solution extracted with diethyl ether (3×) The combined organic layers were washed with brine dried over MgSO4 concentrated The resulting residue was distilled at 200° C.

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

Procedure: To a solution of 3-bromo-4-fluoroacetophenone (10 g, 46 mmol) in THF (100 mL) and methanol (1.0 mL) was added sodium borohydride (2.1 g, 55.5 mmol). The mixture was heated up to 70° C. for 1 h, then cooled down to rt. The reaction was quenched by 100 ml of 1N HCl solution and extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated. The crude product was purified by column chromatography to give 9.8 g of 84A (97% yield). 1H NMR (400 MHz, CDCl3) δ ppm 1.48 (d, J=6.15 Hz, 3H) 7.24-7.33 (m, 1H) 7.59 (dd, J=6.59, 2.20 Hz, 1H). cooled down to rt The reaction was quenched by 100 ml of 1N HCl solution extracted with EtOAc (3×100 mL) The combined organic layers were washed with brine dried over MgSO4 concentrated The crude product was purified by column chromatography

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

Procedure: A solution of 1-(3-bromo-4-fluorophenyl)ethanone (15.0 g, 69 mmol) in tetrahydrofuran (200 mL) was treated with sodium borohydride (5.3 g, 138 mmol) at 0° C. After the addition, the ice bath was removed, and the mixture was stirred at room temperature for 30 minutes and at reflux overnight. After cooling, 1N HCl (10 mL) was slowly added and the reaction mixture was concentrated. The residue was partitioned between ethyl acetate and brine. The organic phase was washed with water, and concentrated. The residue was purified by flash chromatography (30% ethyl acetate in hexane) to provide the title compound. MS (DCI/NH3) m/z 220 (M+H)+. After the addition the ice bath was removed at reflux overnight After cooling 1N HCl (10 mL) was slowly added the reaction mixture was concentrated The residue was partitioned between ethyl acetate and brine The organic phase was washed with water concentrated The residue was purified by flash chromatography (30% ethyl acetate in hexane)

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

Procedure: To a solution of EXAMPLE 412A (1.5 g, 6.8 mmol) and triphenyl phosphine (1.9 g, 7.2 mmol) in dimethylformamide (20 ml) was added bromine (1.1 g, 6.8 mmol) through a syringe. After the addition, the reaction mixture was stirred at room temperature for additional 15 minutes, and partitioned between water (100 ml) and ethyl acetate (200 ml). The organic phase was washed with brine and concentrated. The residue was purified by flash chromatography (2.6% ethyl acetate in hexane) to provide the title compound. MS (DCI/NH4) m/z 282 (M+H)+. After the addition partitioned between water (100 ml) and ethyl acetate (200 ml) The organic phase was washed with brine concentrated The residue was purified by flash chromatography (2.6% ethyl acetate in hexane)

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

Procedure: Synthesized from methyl 1-(5-bromopyrimidin-2-yl)-3-(methylthio)-1H-indole-6-carboxylate (1.0 g, 2.65 mmol) and 1-(3-bromo-4-fluorophenyl)ethanol (0.87 g, 3.98 mmol) analogously to the experimental procedure 289a). Yellow solid. Yield: 1.0 g (89% of theory)