1-amino-3-(2,2,2-trifluoroethyl)imidazolidin-2-one

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

Procedure: Into a 25-mL round-bottom flask, was placed 1-amino-3-(2,2,2-trifluoroethyl)imidazolidin-2-one (90 mg, 0.49 mmol, 1.00 equiv), 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylbenzoic acid (200 mg, 0.48 mmol, 0.97 equiv), EDCI (192 mg, 1.00 mmol, 2.04 equiv), HOBT (135 mg, 1.00 mmol, 2.03 equiv), triethylamine (303 mg, 2.99 mmol, 6.09 equiv), dichloromethane (10 mL). The resulting solution was stirred for 30 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 39 mg (13%) of 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-3-(2,2,2-trifluoroethyl)imidazolidin-1-yl]benzamide as a white solid. (ES, m/z): 583 [M−H]−; 1H NMR (300 MHz, CDCl3) δ 7.89 (s, 1H), 7.43-7.62 (m, 6H), 4.06-4.12 (m, 1H), 3.54-3.89 (m, 7H), 2.47 (s, 3H). Into a 25-mL round-bottom flask, was placed The resulting mixture was concentrated under vacuum This resulted in 39 mg (13%) of 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-3-(2,2,2-trifluoroethyl)imidazolidin-1-yl]benzamide as a white solid

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

Procedure: Into a 250-mL round-bottom flask, was placed a solution of phenyl N-(2-chloroethyl)-N-(2,2,2-trifluoroethyl)carbamate (5.6 g, 19.88 mmol, 1.00 equiv) in ethanol (100 mL), NH2NH2.H2O (10 mL, 80%). The resulting solution was heated to reflux overnight in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate (1:1). This resulted in 0.8 g (22%) of 1-amino-3-(2,2,2-trifluoroethyl)imidazolidin-2-one as colorless oil. (ES, m/z): 184 [M+H]+ Into a 250-mL round-bottom flask, was placed The resulting solution was heated to reflux overnight in an oil bath The resulting mixture was concentrated under vacuum This resulted in 0.8 g (22%) of 1-amino-3-(2,2,2-trifluoroethyl)imidazolidin-2-one as colorless oil

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

Procedure: Into a 25-mL round-bottom flask, was placed 1-amino-3-(2,2,2-trifluoroethyl)imidazolidin-2-one (90 mg, 0.49 mmol, 1.00 equiv), 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylbenzoic acid (200 mg, 0.48 mmol, 0.97 equiv), EDCI (192 mg, 1.00 mmol, 2.04 equiv), HOBT (135 mg, 1.00 mmol, 2.03 equiv), triethylamine (303 mg, 2.99 mmol, 6.09 equiv), dichloromethane (10 mL). The resulting solution was stirred for 30 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 39 mg (13%) of 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-3-(2,2,2-trifluoroethyl)imidazolidin-1-yl]benzamide as a white solid. (ES, m/z): 583 [M−H]−; 1H NMR (300 MHz, CDCl3) δ 7.89 (s, 1H), 7.43-7.62 (m, 6H), 4.06-4.12 (m, 1H), 3.54-3.89 (m, 7H), 2.47 (s, 3H). Into a 25-mL round-bottom flask, was placed The resulting mixture was concentrated under vacuum This resulted in 39 mg (13%) of 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-3-(2,2,2-trifluoroethyl)imidazolidin-1-yl]benzamide as a white solid

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

Procedure: Into a 250-mL round-bottom flask, was placed a solution of phenyl N-(2-chloroethyl)-N-(2,2,2-trifluoroethyl)carbamate (5.6 g, 19.88 mmol, 1.00 equiv) in ethanol (100 mL), NH2NH2.H2O (10 mL, 80%). The resulting solution was heated to reflux overnight in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate (1:1). This resulted in 0.8 g (22%) of 1-amino-3-(2,2,2-trifluoroethyl)imidazolidin-2-one as colorless oil. (ES, m/z): 184 [M+H]+ Into a 250-mL round-bottom flask, was placed The resulting solution was heated to reflux overnight in an oil bath The resulting mixture was concentrated under vacuum This resulted in 0.8 g (22%) of 1-amino-3-(2,2,2-trifluoroethyl)imidazolidin-2-one as colorless oil

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

Procedure: Into a 25-mL round-bottom flask, was placed 1-amino-3-(2,2,2-trifluoroethyl)imidazolidin-2-one (90 mg, 0.49 mmol, 1.00 equiv), 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methylbenzoic acid (200 mg, 0.48 mmol, 0.97 equiv), EDCI (192 mg, 1.00 mmol, 2.04 equiv), HOBT (135 mg, 1.00 mmol, 2.03 equiv), triethylamine (303 mg, 2.99 mmol, 6.09 equiv), dichloromethane (10 mL). The resulting solution was stirred for 30 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:1). This resulted in 39 mg (13%) of 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-3-(2,2,2-trifluoroethyl)imidazolidin-1-yl]benzamide as a white solid. (ES, m/z): 583 [M−H]−; 1H NMR (300 MHz, CDCl3) δ 7.89 (s, 1H), 7.43-7.62 (m, 6H), 4.06-4.12 (m, 1H), 3.54-3.89 (m, 7H), 2.47 (s, 3H). Into a 25-mL round-bottom flask, was placed The resulting mixture was concentrated under vacuum This resulted in 39 mg (13%) of 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-1,2-oxazol-3-yl]-2-methyl-N-[2-oxo-3-(2,2,2-trifluoroethyl)imidazolidin-1-yl]benzamide as a white solid

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

Procedure: Into a 250-mL round-bottom flask, was placed a solution of phenyl N-(2-chloroethyl)-N-(2,2,2-trifluoroethyl)carbamate (5.6 g, 19.88 mmol, 1.00 equiv) in ethanol (100 mL), NH2NH2.H2O (10 mL, 80%). The resulting solution was heated to reflux overnight in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate (1:1). This resulted in 0.8 g (22%) of 1-amino-3-(2,2,2-trifluoroethyl)imidazolidin-2-one as colorless oil. (ES, m/z): 184 [M+H]+ Into a 250-mL round-bottom flask, was placed The resulting solution was heated to reflux overnight in an oil bath The resulting mixture was concentrated under vacuum This resulted in 0.8 g (22%) of 1-amino-3-(2,2,2-trifluoroethyl)imidazolidin-2-one as colorless oil