2-(4-bromophenyl)-N,N-dimethylacetamide

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: The title compound was prepared from 2-(4-bromophenyl)-N,N-dimethylacetamide and 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole using a similar procedure to that described for Example 7.

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

Procedure: A solution of 4-bromophenylacetic acid (960 mg, 4.49 mmol) in dichloromethane (30 ml) was treated in one portion with solid 1,1′-carbonyldiimidazole (730 mg, 4.5 mmol) at 20° C. with stirring under argon. This mixture was allowed to stir at room temperature for 15 minutes. Triethylamine (0.63 ml) was then added followed by dimethylamine hydrochloride (367 mg, 4.5 mmol) and the stirring continued for 1 hour. Most of the solvent was removed under reduced pressure and the residue added to a 20 g isolute silica sep-pak column and eluted from 0-50% ethyl acetate in petroleum ether to give the title compound as a colourless solid (689 mg, 64%). to stir at room temperature for 15 minutes Most of the solvent was removed under reduced pressure the residue added to a 20 g isolute silica sep-pak column eluted from 0-50% ethyl acetate in petroleum ether

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-bromo-N,N-dimethylbenzene acetamide (15 g, 0.06 mole) was added to dry T.H.F. (250 ml) and the solution cooled to -78° C. under nitrogen. Straight chain butyl lithium in hexane (43.3 ml, 0.06 mole) was added dropwise, the temperature being maintained below -70° C. throughout. An orange coloured precipitate formed. After addition, the reaction mixture was maintained near -70° C. for 20 minutes and cyclohexanone (7.5 ml, 0.07 mole) was added. After a further 50 minutes at -78° C. the reaction mixture was poured into stirring saturated ammonium chloride solution. The layers were separated and the aqueous layer extracted with diethyl ether. The combined organic solution was washed with brine, dried over magnesium sulfate and evaporated. The product crystallised and was filtered with isopropanol (9.8 g, m.p. 140 °-144° C.). to dry T.H.F the temperature being maintained below -70° C. throughout formed After addition the reaction mixture was maintained near -70° C. for 20 minutes After a further 50 minutes at -78° C. the reaction mixture was poured The layers were separated the aqueous layer extracted with diethyl ether The combined organic solution was washed with brine dried over magnesium sulfate evaporated The product crystallised was filtered with isopropanol (9.8 g, m.p. 140 °-144° C.)

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

Procedure: The title compound was prepared from 2-(4-bromophenyl)-N,N-dimethylacetamide and 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole using a similar procedure to that described for Example 7.

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

Procedure: A solution of 4-bromophenylacetic acid (960 mg, 4.49 mmol) in dichloromethane (30 ml) was treated in one portion with solid 1,1′-carbonyldiimidazole (730 mg, 4.5 mmol) at 20° C. with stirring under argon. This mixture was allowed to stir at room temperature for 15 minutes. Triethylamine (0.63 ml) was then added followed by dimethylamine hydrochloride (367 mg, 4.5 mmol) and the stirring continued for 1 hour. Most of the solvent was removed under reduced pressure and the residue added to a 20 g isolute silica sep-pak column and eluted from 0-50% ethyl acetate in petroleum ether to give the title compound as a colourless solid (689 mg, 64%). to stir at room temperature for 15 minutes Most of the solvent was removed under reduced pressure the residue added to a 20 g isolute silica sep-pak column eluted from 0-50% ethyl acetate in petroleum ether

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

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-bromo-N,N-dimethylbenzene acetamide (15 g, 0.06 mole) was added to dry T.H.F. (250 ml) and the solution cooled to -78° C. under nitrogen. Straight chain butyl lithium in hexane (43.3 ml, 0.06 mole) was added dropwise, the temperature being maintained below -70° C. throughout. An orange coloured precipitate formed. After addition, the reaction mixture was maintained near -70° C. for 20 minutes and cyclohexanone (7.5 ml, 0.07 mole) was added. After a further 50 minutes at -78° C. the reaction mixture was poured into stirring saturated ammonium chloride solution. The layers were separated and the aqueous layer extracted with diethyl ether. The combined organic solution was washed with brine, dried over magnesium sulfate and evaporated. The product crystallised and was filtered with isopropanol (9.8 g, m.p. 140 °-144° C.). to dry T.H.F the temperature being maintained below -70° C. throughout formed After addition the reaction mixture was maintained near -70° C. for 20 minutes After a further 50 minutes at -78° C. the reaction mixture was poured The layers were separated the aqueous layer extracted with diethyl ether The combined organic solution was washed with brine dried over magnesium sulfate evaporated The product crystallised was filtered with isopropanol (9.8 g, m.p. 140 °-144° C.)

Conditions: temp:120.01; pressure:0.00; stir:

Procedure: 8-(4-fluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-amine (94 mg, 0.40 mmol), 2-(4-bromophenyl)-N,N-dimethylacetamide (103 mg, 0.40 mmol), Cesium carbonate (198 mg, 0.61 mmol), Palladium(II) acetate (9.09 mg, 0.04 mmol) and 2-(Dicyclohexylphosphino)biphenyl (14.18 mg, 0.04 mmol) were added to a 0.5-2 mL microwave vial. The vial was capped and flushed with nitrogen. dioxane (3 mL) was added and the vial was flushed with additional nitrogen before it was heated by microwave irradiation at 120°C for 1.5h. The reaction mixture was cooled to r.t. and water and EtOAc were added and the layers were separated. The aqueous phase was extracted with EtOAc (3x). The combined organic phases were washed with brine, dried (phase separator) and the solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography using a gradient of 0-3% MeOH in EtOAc over 12 min. The desired fractions were combined to result in 2-(4-(8-(4-fluorophenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyridin-2-ylamino)phenyl)-N,N-dimethylacetamide (51.0 mg, 32.0 %)

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

Procedure: The title compound was prepared from 2-(4-bromophenyl)-N,N-dimethylacetamide and 3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazole using a similar procedure to that described for Example 7.