1-(4-chloro-2-hydroxyphenyl)ethanone

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

Procedure: This compound was synthesized from 2′-hydroxy-4′-chloroacetophenone and 4-ethyloxycarbonyldimethylmethyloxybenzaldehyde (starting material 9) according to general method 2 described earlier.

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-chlorophenyl acetate (starting material 2) was mixed with aluminium chloride (3 eq). The mixture was heated at 200° C. for 1 hour. The reaction medium was cooled. to room temperature then poured in ice. The aqueous phase was extracted with methylene chloride which was dried on magnesium sulfate then vacuum evaporated. The reaction medium was cooled to room temperature then poured in ice The aqueous phase was extracted with methylene chloride which was dried on magnesium sulfate vacuum evaporated

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

Procedure: A solution of 4'-chloro-2'-hydroxyacetophenone (1.0 g) in dry DMF (5 ml) was added to a stirred mixture of sodium hydride (0.235 g, 60% dispersion) in dry DMF (5 ml) at 5° C. under nitrogen. After the addition the mixture was stirred at 0° C. for 15 minutes and then at ambient temperature for 1 hour. A solution of iodomethane (0.92 g) in dry DMF (5 ml) was added dropwise to the mixture whilst keeping the temperature below 10° C. The reaction mixture was stirred at ambient temperature for 5 hours and then left to stand for 16 hours. Potassium carbonate solution was added to basify the mixture and the product was extracted into dichloromethane. The combined extracts were dried and evaporated. The residue was dissolved in ether, washed with water, then dried and evaporated to give 4'-chloro-2'-methoxyacetophenone which was sufficiently pure for synthetic use in Example 17. After the addition the mixture at ambient temperature for 1 hour the temperature below 10° C The reaction mixture was stirred at ambient temperature for 5 hours left to stand for 16 hours the product was extracted into dichloromethane The combined extracts were dried evaporated The residue was dissolved in ether washed with water dried evaporated

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

Procedure: A solution of 4'-chloro-2'-hydroxyacetophenone (1.0 g) in dry DMF (5 ml) was added to a stirred mixture of sodium hydride (0.235 g, 60% dispersion) in dry DMF (5 ml) at 5° C. under nitrogen. After the addition the mixture was stirred at 0° C. for 15 minutes and then at ambient temperature for 1 hour. A solution of iodomethane (0.92 g) in dry DMF (5 ml) was added dropwise to the mixture whilst keeping the temperature below 10° C. The reaction mixture was stirred at ambient temperature for 5 hours and then left to stand for 16 hours. Potassium carbonate solution was added to basify the mixture and the product was extracted into dichloromethane. The combined extracts were dried and evaporated. The residue was dissolved in ether, washed with water, then dried and evaporated to give 4'-chloro-2'-methoxyacetophenone which was sufficiently pure for synthetic use in Example 17. After the addition the mixture at ambient temperature for 1 hour the temperature below 10° C The reaction mixture was stirred at ambient temperature for 5 hours left to stand for 16 hours the product was extracted into dichloromethane The combined extracts were dried evaporated The residue was dissolved in ether washed with water dried evaporated

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

Procedure: The title compound was prepared in an analogous manner as Example (60) by 5-(4-fluorophenyl)-6-(piperazin-1-yl)pyrimidin-4-amine reacted with 1-(4-chloro-2-hydroxyphenyl)ethanone. LC-MS: (M+1=428, obsd.=428/430).

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

Procedure: This compound was synthesized from 2′-hydroxy-4′-chloroacetophenone and 4-ethyloxycarbonyldimethylmethyloxybenzaldehyde (starting material 9) according to general method 2 described earlier.

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

Procedure: This compound was synthesized from 2′-hydroxy-4′-chloroacetophenone and 4-ethyloxycarbonyldimethylmethyloxybenzaldehyde (starting material 9) according to general method 2 described earlier.

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-chlorophenyl acetate (starting material 2) was mixed with aluminium chloride (3 eq). The mixture was heated at 200° C. for 1 hour. The reaction medium was cooled to room temperature then poured in ice. The aqueous phase was extracted with methylene chloride which was dried on magnesium sulfate then vacuum evaporated. The reaction medium was cooled to room temperature then poured in ice The aqueous phase was extracted with methylene chloride which was dried on magnesium sulfate vacuum evaporated

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

Procedure: This compound was synthesized from 2′-hydroxy-4′-chloroacetophenone and 4-ethyloxycarbonyldimethylmethyloxybenzaldehyde (starting material 9) according to general method 2 described earlier.

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-chlorophenyl acetate (starting material 2) was mixed with aluminium chloride (3 eq). The mixture was heated at 200° C. for 1 hour. The reaction medium was cooled to room temperature then poured in ice. The aqueous phase was extracted with methylene chloride which was dried on magnesium sulfate then vacuum evaporated. The reaction medium was cooled to room temperature then poured in ice The aqueous phase was extracted with methylene chloride which was dried on magnesium sulfate vacuum evaporated

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-chlorophenyl acetate (starting material 2) was mixed with aluminium chloride (3 eq). The mixture was heated at 200° C. for 1 hour. The reaction medium was cooled to room temperature then poured in ice. The aqueous phase was extracted with methylene chloride which was dried on magnesium sulfate then vacuum evaporated. The reaction medium was cooled to room temperature then poured in ice The aqueous phase was extracted with methylene chloride which was dried on magnesium sulfate vacuum evaporated

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

Procedure: 1-(4-Chloro-2-hydroxyphenyl)ethanone (8.07 g, 47.3 mmol), MeOH (81 mL), 1,1-difluoroacetone (4.89 g, 52.0 mmol), and pyrrolidine (4.30 ml, 52.0 mmol) were stirred at ambient temperature for 45 hours, at 35° C. for 7 hours, then at 50° C. for 3 hours. The reaction mixture was concentrated, diluted with MTBE (75 mL), then washed with water (40 mL), 2N HCl (2×25 mL), brine (20 mL), 2N NaOH (2×20 mL), and brine (2×20 mL). The organic portion was dried (Na2SO4), filtered, and concentrated to give the title compound (9.78 g, 39.7 mmol, 84%) as a brown oil. MS (DCI/NH3) m/z 264 (M+NH4)+. The reaction mixture was concentrated diluted with MTBE (75 mL) washed with water (40 mL), 2N HCl (2×25 mL), brine (20 mL), 2N NaOH (2×20 mL), and brine (2×20 mL) The organic portion was dried (Na2SO4) filtered concentrated