1-(2-chlorophenyl)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:25.01; pressure:0.00; stir:

Procedure: General procedure C was applied to 2-(2-chlorophenyl)-4,4,5,5-tetramethyl-[1,3,2]-dioxaborolane15k(96 mg, 0.4 mmol). The reaction mixture was stirredat room temperature for 16hours giving a conversion of >99% (GCMS) and monoborylated products (16k+zzarising from trace chlorobenzene impurity in the reaction mixture)and 17k in a84:16mixture (1H NMR spectrum).

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

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

Procedure: The crude N′-[5-(2-chloro-benzoyl)-thiazol-2-yl]-N,N-dimethyl-formamidine was dissolved in 10% hydrochloric acid (150 mL) and heated to 70° C. for 4 hours. The precipitate was filtered, washed with ether, and then suspended in a 10% sodium carbonate solution (250 mL). The suspension was stirred for 1 hour and the precipitate was filtered, washed with ether, and dried in air to give (2-amino-thiazol-5-yl)-(2-chloro-phenyl)-methanone as a brown solid (8.5 g, 36 mmol, 55% from 1-(2-chloro-phenyl)-ethanone). ESI-MS m/z calc. 238.0. found; 239.3 (M+1)+ 1H NMR (DMSO): δ: 7.252 (s, 1H), 7.420-7.553 (m, 4H), 8.345 (s, 2H). The precipitate was filtered washed with ether the precipitate was filtered washed with ether dried in air

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

Procedure: The crude N′-[5-(2-chloro-benzoyl)-thiazol-2-yl]-N,N-dimethyl-formamidine was dissolved in 10% aqueous hydrochloric acid (150 mL) and heated to 70° C. for 4 hours. The precipitate was filtered, washed with ether, and then suspended in a 10% aqueous sodium carbonate solution (250 mL). The suspension was stirred for 1 hour and the precipitate was filtered, washed with ether, and dried in air to give (2-amino-thiazol-5-yl)-(2-chloro-phenyl)-methanone as a brown solid (8.5 g, 36 mmol, 55% from 1-(2-chloro-phenyl)-ethanone). ESI-MS m/z calc. 238.0. found 239.3 (M+1)+ 1H NMR (DMSO): δ: 7.252 (s, 1H), 7.420-7.553 (m, 4H), 8.345 (s, 2H). The precipitate was filtered washed with ether the precipitate was filtered washed with ether dried in air

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

Procedure: Bromine (3.8 mL, 65 mmol) was added dropwise to a solution of 1-(2-chloro-phenyl)-ethanone (10. g, 65 mmol) in acetic acid (75 mL) at 0° C. The mixture was then warmed to room temperature and stirred overnight. The mixture was evaporated to dryness and used in the next step without further purification. The mixture was evaporated to dryness used in the next step without further purification

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An oven dried resealable Schlenk tube was evacuated and backfilled with argon and charged with palladium acetate (2.2 mg, 0.01 mmol, 1.0 mol %), 2-(di-tert-butylphosphino)biphenyl (6.0 mg, 0.020 mmol, 2.0 mol %), 2-methoxyphenylboronic acid (228 mg, 1.5 mmol), and potassium phosphate (425 mg, 2.0 mmol). The tube was evacuated and backfilled with argon, and toluene (3 mL) and 2′-chloroacetophenone (0.13 mL, 1.0 mmol) were added through a rubber septum. The tube was sealed with a teflon screwcap, and the reaction mixture was heated to 65° C. with stirring until the starting aryl chloride had been completely consumed as judged by GC analysis. The reaction mixture was then diluted with ether (30 mL) and poured into a separatory funnel. The mixture was washed with water (20 mL), and the aqueous layer was extracted with ether (20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel to afford 201 mg (89%) of the title compound. An oven dried resealable Schlenk tube was evacuated The tube was evacuated were added through a rubber septum had been completely consumed The reaction mixture was then diluted with ether (30 mL) poured into a separatory funnel The mixture was washed with water (20 mL) the aqueous layer was extracted with ether (20 mL) The combined organic layers were washed with brine (20 mL) dried over anhydrous magnesium sulfate filtered concentrated The crude material was purified by flash chromatography on silica gel

Conditions: temp:83.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 5 liter, 3-necked flask equipped with a mechanical stirrer, thermometer, reflux condenser capped with a nitrogen inlet, and a heating mantle were added o-chloroacetophenone (305.8 g), N,N-dimethylformamide dimethyl acetal (707.0 g), and acetonitrile (dried over molecular sieves, 3.0 L) giving an orange solution. The mixture was heated gradually to reflux (83° C.) over 1.5 hours, then maintained at reflux for 18 hours. After the dark red solution was cooled to room temperature, the acetonitrile was evaporated, leaving a heavy red oil. The oil was redissolved in toluene (1L). The toluene was evaporated to afford the crude enamine which was further dried under high vacuum overnight to afford 2'-chloro-3-dimethylaminopropenophenone (422 g) which was used without further purification. To a 5 liter, 3-necked flask equipped with a mechanical stirrer thermometer, reflux condenser capped with a nitrogen inlet giving an orange solution The mixture was heated gradually maintained at reflux for 18 hours After the dark red solution was cooled to room temperature the acetonitrile was evaporated leaving a heavy red oil The toluene was evaporated to afford the crude enamine which was further dried under high vacuum overnight

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2'-chloroacetophenone (309 g), industrial methylated spirit (252 ml), methylamine (33% w/w solution in industrial methylated spirit, 1085 ml) and copper lining powder (2.7 g) was stirred in a sealed pressure vessel for 3 hours at 80° C. The reaction vessel was allowed to cool to 40° and the mixture was washed out of the vessel with industrial methylated spirit (60 ml). The combined reaction mixture and washing were stirred at 50 to 55°, a solution of sodium sulphide trihydrate (6.6 g) in water (45 ml) was added dropwise and the stirring and heating were continued for 15 minutes. The mixture was filtered through diatomaceous earth (sold under the trade name HYFLO SUPERCEL) and the filter bed washed with industrial methylated spirit (300 ml). The combined filtrate and washing were evaporated under reduced pressure to give an oil which was added to hydrochloric acid (5M, 900 ml) and then stirred and heated under reflux for 2 hours. The mixture was cooled to 30°, washed with hexane (2×990 ml) and then adjusted to pH 2 to 3 by addition of aqueous sodium hydroxide (5M, 750 ml) whilst maintaining the temperature at 30 to 35°. The mixture was then extracted with dichloromethane (990 ml) and the extract evaporated under reduced pressure to give the novel compound 2'-(methylamino)acetophenone, m.p. 34°-35°. to cool to 40° the mixture was washed out of the vessel with industrial methylated spirit (60 ml) The combined reaction mixture washing were stirred at 50 to 55° a solution of sodium sulphide trihydrate (6.6 g) in water (45 ml) was added dropwise the stirring and heating were continued for 15 minutes The mixture was filtered through diatomaceous earth ( washed with industrial methylated spirit (300 ml) The combined filtrate and washing were evaporated under reduced pressure to give an oil which stirred heated under reflux for 2 hours The mixture was cooled to 30° washed with hexane (2×990 ml) adjusted to pH 2 to 3 by addition of aqueous sodium hydroxide (5M, 750 ml) whilst maintaining the temperature at 30 to 35° The mixture was then extracted with dichloromethane (990 ml) the extract evaporated under reduced pressure