1-(4-fluorophenyl)ethanol

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

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

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

Procedure: 0.5 g of 1-(4-fluorophenyl)ethanol is dissolved in 20 cm3 of dichloromethane, under an inert atmosphere, at a temperature close to 20° C. 1.24 cm3 of pure bromo(trimethyl)silane are introduced in two lots to the reaction mixture. The latter is stirred at a temperature close to 20° C. for 48 h, then it is washed with a saturated aqueous solution of sodium chloride, dried over a phase separation cartridge and concentrated using a rotary evaporator under reduced pressure (5 kPa). The 700 mg of crude product obtained are purified by filtration through a silica pellet (eluent: 10% ethyl acetate/90% cyclohexane). After concentrating the fractions under reduced pressure, 439 mg of 1-(1-bromoethyl)-4-fluorobenzene are obtained in the form of a colorless thick oil. close to 20° C close to 20° C. for 48 h it is washed with a saturated aqueous solution of sodium chloride dried over a phase separation cartridge concentrated a rotary evaporator under reduced pressure (5 kPa)

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

Procedure: To an oven-dried round bottom flask was added toluene (1 mL), the product of Step D of Example 114 (0.050 g; 0.134 mmol); 1-(4-flourophenyl)ethanol (0.070 mL; 0.536 mmol), and cesium carbonate (0.218 g; 0.670 mmol). The reaction mixture was heated at 100° C. and stirred for 16 hours. The reaction mixture was allowed to cool to room temperature, then it was partitioned between ethyl acetate and 2N aq. NaOH solution. The organic portion was separated and washed with more 2N aq. NaOH solution (2×), brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification was done by MPLC (silica gel; 0-10% ethyl acetate:hexane) to afford 0.051 g of the desired product: m/e=355 (M-1-(4-flourophenyl)ethyl group) Rt=4.9 min on LCMS. to cool to room temperature it was partitioned between ethyl acetate and 2N aq. NaOH solution The organic portion was separated washed with more 2N aq. NaOH solution (2×), brine dried (Na2SO4) filtered concentrated in vacuo Purification

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

Procedure: The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and 1-(4-fluorophenyl)ethanol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 1.65 (3H, d, J=6.4 Hz), 5.24 (1H, q, J=6.4 Hz), 5.44 (1H, d, J=2.0 Hz), 6.95-7.00 (2H, m), 7.27-7.30 (2H, m), 7.35 (1H, dd, J=0.8 Hz, J=5.2 Hz), 7.41 (1H, d, J=2.0 Hz), 7.97 (1H, s), 8.66 (1H, d, J=4.8 Hz). [M+H] Calc'd for C17H13FN4O, 309; Found, 309.

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

Procedure: 2-Methylthio-5-(4-chlorophenyl)-4-(2,4-dichlorophenyl)pyrimidine from Reference Example 3 was reacted with α-methyl-4-fluorobenzyl alcohol according to the procedure described in Example 59 to afford 2-(α-methyl-4-fluorobenzyloxy)-4-(2,4-dichlorophenyl)-5-(4-chlorophenyl)pyrimidine (HRf): HPLC/MS: m/e=473 (M++1); Rt=4.80 min; 1H-NMR 400 MHz (CDCl3): δ 1.76 (d, J=9 Hz, 3H), 6.22-6.30 (dd, J=6 Hz, J=9 Hz, 1H), 6.90-7.05 (m, 4H), 7.15-7.18 (d, J=9 Hz, 2H), 7.21-7.23 (m, 3H), 7.38 (d, 1H), 7.45-7.52 (m, 2H), 8.58 (m, 1H).

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

Procedure: 2-Methylthio-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)pyrimidine from Reference Example 3 was reacted with α-methyl-4-fluorobenzyl alcohol according to the procedure described in Example 59 to afford 2-(α-methyl-4-fluorobenzyloxy-)-4-(4-chlorophenyl)-5-(2,4-dichlorophenyl)pyrimidine. (HRf): HPLC/MS: m/e=473 (M++1); Rt=4.91 min; 1H-NMR 400 MHz (CDCl3): δ 1.78 (d, J=9 Hz, 3H), 6.22-6.30 (dd, J=6 Hz, J=9 Hz, 1H), 7.02 (m, 3H), 7.20-7.25 (m, 5H), 7.50-7.59 (m, 3H), 8.40 (m, 1H).

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

Procedure: 2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (85 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (114 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluoro-α-methylbenzyl alcohol (54 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (45 mg, yield 35%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 15 min with heating under reflux for 2 hr After the completion of the reaction before distilled water was added The mixture was subjected to separatory extraction with chloroform by washing with a 1 N aqueous hydrochloric acid solution and saturated brine The washed solution was dried over sodium sulfate was concentrated The residue was purified on a column

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

Procedure: 2-Chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]-aniline (85 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (114 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluoro-α-methylbenzyl alcohol (54 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (45 mg, yield 35%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 15 min with heating under reflux for 2 hr After the completion of the reaction before distilled water was added The mixture was subjected to separatory extraction with chloroform by washing with a 1 N aqueous hydrochloric acid solution and saturated brine The washed solution was dried over sodium sulfate was concentrated The residue was purified on a column

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

Procedure: 4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (80 mg) was added to toluene/triethylamine=10/1 (8 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (120 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluoro-α-methylbenzyl alcohol (57 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (59 mg, yield 47%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 15 min with heating under reflux for 2 hr After the completion of the reaction before distilled water was added The mixture was subjected to separatory extraction with chloroform by washing with a 1 N aqueous hydrochloric acid solution and saturated brine The washed solution was dried over sodium sulfate was concentrated The residue was purified on a column

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (123 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluoro-α-methylbenzyl alcohol (58 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (87 mg, yield 64%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 15 min with heating under reflux for 2 hr After the completion of the reaction before distilled water was added The mixture was subjected to separatory extraction with chloroform by washing with a 1 N aqueous hydrochloric acid solution and saturated brine The washed solution was dried over sodium sulfate was concentrated The residue was purified on a column

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

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (90 mg) was added to toluene/triethylamine=10/1 (9 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (123 mg) in methylene chloride was then added to the solution, and the mixture was heated under reflux for 15 min. Subsequently, 4-fluoro-α-methylbenzyl alcohol (58 mg) was added thereto, and the mixture was further stirred with heating under reflux for 2 hr. After the completion of the reaction, the reaction solution was allowed to cool to room temperature before distilled water was added thereto. The mixture was subjected to separatory extraction with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution and saturated brine. The washed solution was dried over sodium sulfate and was concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (87 mg, yield 64%). the mixture was heated under reflux to prepare a solution the mixture was heated under reflux for 15 min with heating under reflux for 2 hr After the completion of the reaction before distilled water was added The mixture was subjected to separatory extraction with chloroform by washing with a 1 N aqueous hydrochloric acid solution and saturated brine The washed solution was dried over sodium sulfate was concentrated The residue was purified on a column