imidazolidin-4-one;hydrochloride

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

Procedure: Into a 100-mL round-bottom flask, was placed 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylbenzoic acid (900 mg, 1.99 mmol, 1.00 equiv), N,N-dimethylformamide (10 mL), HATU (1.1 g, 2.89 mmol, 1.45 equiv), DIEA (770 mg, 5.96 mmol, 2.99 equiv), imidazolidin-4-one hydrochloride (489 mg, 3.99 mmol, 2.00 equiv). The resulting solution was stirred for 2 h at rt. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 3×10 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×20 mL of brine. The resulting organic phase was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/30-1/10). This resulted in 600 mg (58%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a light yellow solid. Into a 100-mL round-bottom flask, was placed The reaction was then quenched by the addition of 10 mL of water The resulting solution was extracted with 3×10 mL of ethyl acetate The resulting mixture was washed with 3×20 mL of brine The resulting organic phase was concentrated under vacuum This resulted in 600 mg (58%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a light yellow solid

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

Procedure: Into a 25-mL round-bottom flask, was placed 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(2,2,2-trifluoroethyl)benzoic acid (200 mg, 0.38 mmol, 1.00 equiv), N,N-dimethylformamide (10 mL), HATU (292 mg, 0.77 mmol, 2.00 equiv), DIEA (99 mg, 0.77 mmol, 1.94 equiv), imidazolidin-4-one hydrochloride (94 mg, 0.77 mmol, 1.98 equiv). The resulting solution was stirred for 2 h at r t. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 2×10 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×20 mL of brine. The resulting mixture was concentrated under vacuum. The residue was applied onto a TLC plate with ethyl acetate/petroleum ether (2:1). This resulted in 150 mg (60%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(2,2,2-trifluoroethyl)phenyl)carbonyl]imidazolidin-4-one as yellow oil. Into a 25-mL round-bottom flask, was placed The reaction was then quenched by the addition of 10 mL of water The resulting solution was extracted with 2×10 mL of ethyl acetate The resulting mixture was washed with 3×20 mL of brine The resulting mixture was concentrated under vacuum This resulted in 150 mg (60%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(2,2,2-trifluoroethyl)phenyl)carbonyl]imidazolidin-4-one as yellow oil

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 50-mL round-bottom flask, was placed a solution of 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)benzoic acid (300 mg, 0.64 mmol, 1.00 equiv) in N,N-dimethylformamide (2 mL), HATU (483 mg, 1.27 mmol, 2.00 equiv), DIEA (164 mg, 1.27 mmol, 2.00 equiv), imidazolidin-4-one hydrochloride (155 mg, 1.26 mmol, 2.00 equiv). The resulting solution was stirred for 3 h at 20° C. The resulting solution was diluted with 50 mL of brine. The resulting solution was extracted with 3×50 mL of ethyl acetate and the organic layers combined. The mixture was dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with PE/EA (10:1). This resulted in 320 mg (93%) of 1-([4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)imidazolidin-4-one as light yellow oil. Into a 50-mL round-bottom flask, was placed The resulting solution was extracted with 3×50 mL of ethyl acetate The mixture was dried over sodium sulfate concentrated under vacuum This resulted in 320 mg (93%) of 1-([4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)imidazolidin-4-one as light yellow oil

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

Procedure: Into a 100-mL round-bottom flask, was placed 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylbenzoic acid (452 mg, 1.00 mmol, 1.00 equiv), dichloromethane (50 mL), EDCI (384 mg, 2.00 mmol, 2.00 equiv), HOBt (270 mg, 2.00 mmol, 2.00 equiv), TEA (303 mg, 2.99 mmol, 3.00 equiv), imidazolidin-4-one hydrochloride (135 mg, 1.10 mmol, 1.00 equiv). The resulting solution was stirred overnight at room temperature. The resulting solution was diluted with 100 mL of DCM. The resulting mixture was washed with 3×50 mL of brine. The mixture was dried over anhydrous sodium sulfate. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:2). This resulted in 200 mg (38%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a light yellow solid. Into a 100-mL round-bottom flask, was placed The resulting mixture was washed with 3×50 mL of brine The mixture was dried over anhydrous sodium sulfate The resulting mixture was concentrated under vacuum This resulted in 200 mg (38%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a light yellow solid

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

Procedure: Into a 100-mL 3-necked round-bottom flask, was placed a solution of 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-methyl-4,5-dihydro-1,2-oxazol-3-yl]-2-methylbenzoic acid (100 mg, 0.25 mmol, 1.00 equiv) in dichloromethane (5 mL), imidazolidin-4-one hydrochloride (27.05 mg, 0.22 mmol, 1.00 equiv), HOBt (32.92 mg, 0.24 mmol, 1.10 equiv), triethylamine (33.59 mg, 0.33 mmol, 2.10 equiv), EDCI (63.85 mg, 0.33 mmol, 1.50 equiv). The resulting solution was stirred overnight at room temperature. The resulting solution was diluted with 20 mL of water. The resulting solution was extracted with 3×10 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5-1:1). This resulted in 80 mg (68%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-methyl-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a white solid. Into a 100-mL 3-necked round-bottom flask, was placed The resulting solution was extracted with 3×10 mL of dichloromethane dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 80 mg (68%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-methyl-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a white solid

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

Procedure: Into a 100-mL round-bottom flask, was placed 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylbenzoic acid (900 mg, 1.99 mmol, 1.00 equiv), N,N-dimethylformamide (10 mL), HATU (1.1 g, 2.89 mmol, 1.45 equiv), DIEA (770 mg, 5.96 mmol, 2.99 equiv), imidazolidin-4-one hydrochloride (489 mg, 3.99 mmol, 2.00 equiv). The resulting solution was stirred for 2 h at rt. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 3×10 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×20 mL of brine. The resulting organic phase was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/30-1/10). This resulted in 600 mg (58%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a light yellow solid. Into a 100-mL round-bottom flask, was placed The reaction was then quenched by the addition of 10 mL of water The resulting solution was extracted with 3×10 mL of ethyl acetate The resulting mixture was washed with 3×20 mL of brine The resulting organic phase was concentrated under vacuum This resulted in 600 mg (58%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a light yellow solid

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

Procedure: Into a 25-mL round-bottom flask, was placed 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(2,2,2-trifluoroethyl)benzoic acid (200 mg, 0.38 mmol, 1.00 equiv), N,N-dimethylformamide (10 mL), HATU (292 mg, 0.77 mmol, 2.00 equiv), DIEA (99 mg, 0.77 mmol, 1.94 equiv), imidazolidin-4-one hydrochloride (94 mg, 0.77 mmol, 1.98 equiv). The resulting solution was stirred for 2 h at r t. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 2×10 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×20 mL of brine. The resulting mixture was concentrated under vacuum. The residue was applied onto a TLC plate with ethyl acetate/petroleum ether (2:1). This resulted in 150 mg (60%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(2,2,2-trifluoroethyl)phenyl)carbonyl]imidazolidin-4-one as yellow oil. Into a 25-mL round-bottom flask, was placed The reaction was then quenched by the addition of 10 mL of water The resulting solution was extracted with 2×10 mL of ethyl acetate The resulting mixture was washed with 3×20 mL of brine The resulting mixture was concentrated under vacuum This resulted in 150 mg (60%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(2,2,2-trifluoroethyl)phenyl)carbonyl]imidazolidin-4-one as yellow oil

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 50-mL round-bottom flask, was placed a solution of 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)benzoic acid (300 mg, 0.64 mmol, 1.00 equiv) in N,N-dimethylformamide (2 mL), HATU (483 mg, 1.27 mmol, 2.00 equiv), DIEA (164 mg, 1.27 mmol, 2.00 equiv), imidazolidin-4-one hydrochloride (155 mg, 1.26 mmol, 2.00 equiv). The resulting solution was stirred for 3 h at 20° C. The resulting solution was diluted with 50 mL of brine. The resulting solution was extracted with 3×50 mL of ethyl acetate and the organic layers combined. The mixture was dried over sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with PE/EA (10:1). This resulted in 320 mg (93%) of 1-([4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)imidazolidin-4-one as light yellow oil. Into a 50-mL round-bottom flask, was placed The resulting solution was extracted with 3×50 mL of ethyl acetate The mixture was dried over sodium sulfate concentrated under vacuum This resulted in 320 mg (93%) of 1-([4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(trifluoromethyl)phenyl]carbonyl)imidazolidin-4-one as light yellow oil

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

Procedure: Into a 100-mL round-bottom flask, was placed 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylbenzoic acid (452 mg, 1.00 mmol, 1.00 equiv), dichloromethane (50 mL), EDCI (384 mg, 2.00 mmol, 2.00 equiv), HOBt (270 mg, 2.00 mmol, 2.00 equiv), TEA (303 mg, 2.99 mmol, 3.00 equiv), imidazolidin-4-one hydrochloride (135 mg, 1.10 mmol, 1.00 equiv). The resulting solution was stirred overnight at room temperature. The resulting solution was diluted with 100 mL of DCM. The resulting mixture was washed with 3×50 mL of brine. The mixture was dried over anhydrous sodium sulfate. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:2). This resulted in 200 mg (38%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a light yellow solid. Into a 100-mL round-bottom flask, was placed The resulting mixture was washed with 3×50 mL of brine The mixture was dried over anhydrous sodium sulfate The resulting mixture was concentrated under vacuum This resulted in 200 mg (38%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a light yellow solid

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

Procedure: Into a 100-mL 3-necked round-bottom flask, was placed a solution of 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-methyl-4,5-dihydro-1,2-oxazol-3-yl]-2-methylbenzoic acid (100 mg, 0.25 mmol, 1.00 equiv) in dichloromethane (5 mL), imidazolidin-4-one hydrochloride (27.05 mg, 0.22 mmol, 1.00 equiv), HOBt (32.92 mg, 0.24 mmol, 1.10 equiv), triethylamine (33.59 mg, 0.33 mmol, 2.10 equiv), EDCI (63.85 mg, 0.33 mmol, 1.50 equiv). The resulting solution was stirred overnight at room temperature. The resulting solution was diluted with 20 mL of water. The resulting solution was extracted with 3×10 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5-1:1). This resulted in 80 mg (68%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-methyl-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a white solid. Into a 100-mL 3-necked round-bottom flask, was placed The resulting solution was extracted with 3×10 mL of dichloromethane dried over anhydrous sodium sulfate concentrated under vacuum This resulted in 80 mg (68%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-methyl-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a white solid

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

Procedure: Into a 100-mL round-bottom flask, was placed 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylbenzoic acid (900 mg, 1.99 mmol, 1.00 equiv), N,N-dimethylformamide (10 mL), HATU (1.1 g, 2.89 mmol, 1.45 equiv), DIEA (770 mg, 5.96 mmol, 2.99 equiv), imidazolidin-4-one hydrochloride (489 mg, 3.99 mmol, 2.00 equiv). The resulting solution was stirred for 2 h at rt. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 3×10 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×20 mL of brine. The resulting organic phase was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1/30-1/10). This resulted in 600 mg (58%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a light yellow solid. Into a 100-mL round-bottom flask, was placed The reaction was then quenched by the addition of 10 mL of water The resulting solution was extracted with 3×10 mL of ethyl acetate The resulting mixture was washed with 3×20 mL of brine The resulting organic phase was concentrated under vacuum This resulted in 600 mg (58%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylphenyl)carbonyl]imidazolidin-4-one as a light yellow solid

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

Procedure: Into a 25-mL round-bottom flask, was placed 4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(2,2,2-trifluoroethyl)benzoic acid (200 mg, 0.38 mmol, 1.00 equiv), N,N-dimethylformamide (10 mL), HATU (292 mg, 0.77 mmol, 2.00 equiv), DIEA (99 mg, 0.77 mmol, 1.94 equiv), imidazolidin-4-one hydrochloride (94 mg, 0.77 mmol, 1.98 equiv). The resulting solution was stirred for 2 h at r t. The reaction was then quenched by the addition of 10 mL of water. The resulting solution was extracted with 2×10 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×20 mL of brine. The resulting mixture was concentrated under vacuum. The residue was applied onto a TLC plate with ethyl acetate/petroleum ether (2:1). This resulted in 150 mg (60%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(2,2,2-trifluoroethyl)phenyl)carbonyl]imidazolidin-4-one as yellow oil. Into a 25-mL round-bottom flask, was placed The reaction was then quenched by the addition of 10 mL of water The resulting solution was extracted with 2×10 mL of ethyl acetate The resulting mixture was washed with 3×20 mL of brine The resulting mixture was concentrated under vacuum This resulted in 150 mg (60%) of 1-[(4-[5-[3-chloro-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-(2,2,2-trifluoroethyl)phenyl)carbonyl]imidazolidin-4-one as yellow oil