2-bromo-1-(2-chloro-4-fluorophenyl)ethanone

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

Procedure: 5-(2-Chloro-4-fluorophenyl)-7-methyl-4-(1H-1,2,4-triazol-1-yl)imidazo[5,1-f][1,2,4]triazine was prepared in similar fashion to C6 in Example 1, by employing 2-bromo-1-(2-chloro-4-fluorophenyl)ethanone.

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

Procedure: Combine formic acid (98-100%; 0.30 mL, 8 mmol) and 2-benzylaminoethanol (1.21 g, 8 mmol) and cool the resulting mixture with an ice bath. Add 2-bromo-1-(2-chloro-4-fluoro-phenyl)ethanone (1.0 g, 4 mmol); heat the mixture to reflux; and stir at that temperature for 20 h. Dilute the mixture with DCM and wash with saturated aqueous Na2CO3 solution. Dry organic phases over MgSO4; filter; collect the filtrate; and concentrate under reduced pressure. Purify via flash column chromatography eluting with a gradient of 0-20% methyl tertiary-butyl ether in hexanes. Combine the product fractions and remove the solvents under reduced pressure to give the title compound as a yellow oil (1.22 g, 43%). MS (m/z): 306 (M+1). heat the mixture to reflux wash with saturated aqueous Na2CO3 solution filter collect the filtrate and concentrate under reduced pressure Purify via flash column chromatography eluting with a gradient of 0-20% methyl tertiary-butyl ether in hexanes Combine the product fractions and remove the solvents under reduced pressure

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

Procedure: 5-(2-Chloro-4-fluorophenyl)-7-methyl-4-(1H-1,2,4-triazol-1-yl)imidazo[5,1-f][1,2,4]triazine was prepared in similar fashion to C6 in Example 1, by employing 2-bromo-1-(2-chloro-4-fluorophenyl)ethanone.

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

Procedure: To a stirred solution of 78.7 parts of 2-bromo-1-(2-chloro-4-fluorophenyl)ethanone in 140 parts of 1,1'-oxybisethane are added carefully 106.4 parts of 1H-imidazole. Upon completion, there are added 180 parts of N,N-dimethylformamide and the whole is stirred for 2 hours at 50° C. After the addition of water, the product is extracted twice with trichloromethane. The combined extracts are washed three times with water, dried, filtered and evaporated. The residue is converted into the hydrochloride salt in 4-methyl-2-pentanone, 2,2'-oxybispropane and 2-propanol. The salt is filtered off and crystallized from a mixture of ethanol and 2,2'-oxybispropane, yielding 1.5 parts of 1-(2-chloro-4-fluorophenyl)-2-(1H-imidazol-1-yl)ethanone hydrochloride; mp. 197.4° C. the product is extracted twice with trichloromethane The combined extracts are washed three times with water dried filtered evaporated The salt is filtered off crystallized from a mixture of ethanol and 2,2'-oxybispropane

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

Procedure: 5-(2-Chloro-4-fluorophenyl)-7-methyl-4-(1H-1,2,4-triazol-1-yl)imidazo[5,1-f][1,2,4]triazine was prepared in similar fashion to C6 in Example 1, by employing 2-bromo-1-(2-chloro-4-fluorophenyl)ethanone.

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

Procedure: To a stirred solution of 78.7 parts of 2-bromo-1-(2-chloro-4-fluorophenyl)ethanone in 140 parts of 1,1'-oxybisethane are added carefully 106.4 parts of 1H-imidazole. Upon completion, there are added 180 parts of N,N-dimethylformamide and the whole is stirred for 2 hours at 50° C. After the addition of water, the product is extracted twice with trichloromethane. The combined extracts are washed three times with water, dried, filtered and evaporated. The residue is converted into the hydrochloride salt in 4-methyl-2-pentanone, 2,2'-oxybispropane and 2-propanol. The salt is filtered off and crystallized from a mixture of ethanol and 2,2'-oxybispropane, yielding 1.5 parts of 1-(2-chloro-4-fluorophenyl)-2-(1H-imidazol-1-yl)ethanone hydrochloride; mp. 197.4° C. the product is extracted twice with trichloromethane The combined extracts are washed three times with water dried filtered evaporated The salt is filtered off crystallized from a mixture of ethanol and 2,2'-oxybispropane

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

Procedure: 5-(2-Chloro-4-fluorophenyl)-7-methyl-4-(1H-1,2,4-triazol-1-yl)imidazo[5,1-f][1,2,4]triazine was prepared in similar fashion to C6 in Example 1, by employing 2-bromo-1-(2-chloro-4-fluorophenyl)ethanone.

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

Procedure: Combine formic acid (98-100%; 0.30 mL, 8 mmol) and 2-benzylaminoethanol (1.21 g, 8 mmol) and cool the resulting mixture with an ice bath. Add 2-bromo-1-(2-chloro-4-fluoro-phenyl)ethanone (1.0 g, 4 mmol); heat the mixture to reflux; and stir at that temperature for 20 h. Dilute the mixture with DCM and wash with saturated aqueous Na2CO3 solution. Dry organic phases over MgSO4; filter; collect the filtrate; and concentrate under reduced pressure. Purify via flash column chromatography eluting with a gradient of 0-20% methyl tertiary-butyl ether in hexanes. Combine the product fractions and remove the solvents under reduced pressure to give the title compound as a yellow oil (1.22 g, 43%). MS (m/z): 306 (M+1). heat the mixture to reflux wash with saturated aqueous Na2CO3 solution filter collect the filtrate and concentrate under reduced pressure Purify via flash column chromatography eluting with a gradient of 0-20% methyl tertiary-butyl ether in hexanes Combine the product fractions and remove the solvents under reduced pressure